Cancer of unknown primary (CUP)

What is cancer of unknown primary (CUP)?

Primary cancer means where the cancer started. The part of the body where the cancer first started to grow is called the primary site. The cancer type is usually named after the part of the body where it first started to grow. For example, a cancer that starts in the lung is called a primary lung cancer.

A secondary cancer happens when cancer cells separate from a primary site and spread to another part of the body. The cancer cells travel through the blood or lymphatic system and form a new cancer somewhere else in the body.

A secondary cancer is also called a metastasis or metastatic cancer. It is made up of the same type of cancer cells that formed the primary cancer. For example, a cancer that starts in the lungs and spreads to the liver is made up of lung cancer cells, not liver cancer cells.

Cancer of unknown primary (CUP) means that your doctor is not sure where the cancer started. They have found a secondary cancer but have not been able to find the primary cancer. People with CUP sometimes have secondary cancer in more than 1 part of the body

With CUP, doctors cannot always tell which part of the body the cancer cells are from. But cancers are made up of different types of cells. These can be grouped based on the type of cells they are made up of. Knowing the type of cell can give the doctors a better idea about where the cancer may have started. This helps them to plan the best treatment.

We have more information about CUP and different cell types.

Reasons the primary cancer cannot be found

Sometimes doctors cannot find out where the primary cancer started. This may be because:

  • the primary cancer is too small to be seen on scans
  • the primary cancer is hidden by a larger secondary cancer
  • the body’s immune system has destroyed it, but it has already spread.

Doctors might stop looking for the primary cancer if:

  • you are not feeling well enough to have tests
  • further test results are unlikely to change your treatment plan.
Related pages

Symptoms of CUP

Symptoms of cancer of unknown primary (CUP) depend on where the secondary cancer (or cancers) is in the body. The most common places for cancer to spread to are the:

General symptoms of cancer

General symptoms of cancer include:

  • unexplained weight loss
  • loss of appetite
  • feeling extremely tired all the time
  • pain that does not go away or has no obvious cause
  • looking pale, and feeling tired and breathless – this may be caused by a low level of red blood cells (anaemia).

All the symptoms mentioned here can be caused by conditions other than cancer. But it is important to see your GP and get them checked.


If you have symptoms, you usually start by seeing your GP. They will examine you and ask about your symptoms. If they think you might have cancer, they may refer you to a specialist for tests. Or if you have symptoms that are making you very unwell, you may be admitted to hospital straight away. In this situation, you will have tests while you are staying in hospital as an inpatient.

The first specialist doctor you see and the tests you have depend on your symptoms. For example,

  • if you have bowel or stomach symptoms, your GP will refer you to a gastroenterologist. They treat problems of the digestive system.
  • if you have kidney or bladder symptoms, you will see a urologist. They treat problems of the urinary system.

Doctors may look for the most common types of primary cancers first. The tests might show you have cancer, but the doctors still may not know where the cancer started. In this situation, the GP may refer you directly to a particular hospital team. This could be:

  • the malignancy of unknown origin (MUO) team
  • the cancer of unknown primary (CUP) team
  • a rapid diagnostic centre.

The specialist team will arrange any tests you need. The tests you have depend on your symptoms. Your doctor will use national guidelines to decide which tests are right for you. The results of one test may suggest that another one would be useful.

You might have some of the following tests and scans:

  • Blood tests

    Blood tests can help doctors find out how organs such as the liver and kidneys are working. They are also used to find out the number of different blood cells you are producing (your full blood count).This information can help your doctors decide which area of the body to scan. For example, if the liver or kidneys are not working properly, your doctor may decide to scan them.

  • X-rays and scans

    You may have x-rays or scans to help find a primary cancer, or understand more about the type of cancer you have. We have more information about x-rays, mammograms, CT scans, PET-CT scans, MRI scans, and ultrasound scans in our A-Z of tests.

  • Cameras that look inside the body (endoscopy)

    An endoscopy is a test that looks inside the body using a thin, flexible tube with a camera on the end. This test may have different names depending on the area of the body. If you know the name of the test you are having, you can find it in our A-Z of tests. The most common types of  include upper gastro-intestinal endoscopy, bronchoscopy, nasendoscopy, laryngoscopy, colonoscopy, cystoscopy and hysteroscopy.

  • Laparoscopy

    A laparoscopy is a small operation to look at organs inside your tummy (abdomen).

  • Biopsy

    If tests show that you might have cancer, you may have a biopsy. A biopsy means taking a sample of tissue or cells from an abnormal area. The sample is checked under a microscope for cancer cells. Some tests on a biopsy sample may give doctors more information about the type of cancer you have.

  • Removing fluid for testing

    You may have a build-up of fluid in your body. If the fluid collects around the lung, it is called a pleural effusion. A collection of fluid around the tummy (abdomen) is called ascites. Doctors can take a sample of this fluid and check it for cancer cells.
    You have a local anaesthetic injection to numb the area. The doctor uses a needle to remove some fluid. Sometimes the doctor uses an ultrasound scan to help find the best area to get a sample from.

  • Bone marrow test

    You might have a bone marrow biopsy to check whether the cancer is affecting the bone marrow. Bone marrow is a spongy material in the middle of our bones. It is where blood cells are made.

Other tests on the biopsy

Some other tests can be done on a biopsy sample. They may give doctors more information about the type of cancer you have.

You might have some of the following tests and scans:

  • Immunohistochemistry test

    This test uses antibodies to find out whether there are particular proteins on the surface of the cell. These may be linked to some cancer types.

  • Cytogenetic test

    This test looks at the changes in the chromosomes in a cell. Changes in the structure of some chromosomes can be linked to some cancer types.

  • Hormone and protein receptor test

    This test looks at cancer cells with receptors. Some cancer cells have receptors which certain types of hormones or proteins to attach to. Identifying these may help doctors find out where the cancer cells came from.

  • Gene expression-based profiling (GEBP)

    GEBP looks for patterns of genes in the secondary cancer tissue. These patterns can help doctors find out what the primary cancer might be. This can help them decide which other tests you should have and which treatments are most suitable for you.
    At the moment, gene profiling tests for people with CUP are not usually available on the NHS. But you may be able to have them as part of a clinical trial. You can find further information about gene expression-based profiling on the Cancer of Unknown Primary Foundation website.

Waiting for test results

Waiting for test results can be a difficult time. It may take from a few days to a couple of weeks for the results to be ready. You may find it helpful to talk with a partner, family member or close friend. Your specialist nurse or a support organisation can also provide support. Or you can talk to one of our cancer support specialists for free on 0808 808 00 00 (7 days a week, 8am to 8pm).

Being diagnosed with cancer of unknown primary can make you feel shocked, frightened, angry or upset. There is no right or wrong way to feel. It may help to get support from family, friends or a support organisation.

Macmillan is also here to support you. If you would like to talk, you can:

Treatment for CUP

When CUP is diagnosed, cancer has already spread from one part of the body to another. In many cases, this means the cancer is already advanced. It is not usually possible to cure cancer that is advanced and has spread to other parts of the body. The aim of treatment for CUP is to try to:

  • control the cancer
  • help you live longer
  • treat your symptoms
  • improve your quality of life.

A team of specialists will meet to discuss the best possible treatment for you. This is called a multidisciplinary team MDT. Your cancer doctor or specialist nurse will explain the different treatments and their side effects. They will also talk to you about things to consider when making treatment decisions.

We have more information about treating and managing symptoms of CUP that explains when each treatment may be used. You may have one treatment or a combination of treatments. You may be offered some as part of a clinical trial.

After treatment

When your treatment has finished, you will have regular check-ups. You may also have follow-up scans. How often you have them will depend on your treatment plan:

  • If the aim of treatment was to cure the cancer, you may see your cancer doctor or specialist nurse every few months for up to two years.
  • If the aim of treatment was to control the cancer, you may see your cancer doctor or specialist nurse less often.

Your cancer doctor and specialist nurse will give you advice on what to look out for. If you have any problems or notice new symptoms between check-ups, tell them as soon as possible.

About our information

  • References

    Below is a sample of the sources used in our chondrosarcoma information. If you would like more information about the sources we use, please contact us at

    Fizazi K et al. Cancers of unknown primary site. ESMO clinical practice guidelines for diagnosis, treatment and follow up. 2015. Annals of oncology 26 (supplement 5): v133-v138.

    National Institute for Health and Care Excellence (NICE). Metastatic malignant disease of unknown primary origin in adults: diagnosis and management. 2010.

    UK Oncology Nursing Society (UKONS). Acute oncology initial management guidelines. [Internet], 2018. Available from: [accessed March 2022].

  • Reviewers

    This information has been written, revised and edited by Macmillan Cancer Support’s Cancer Information Development team. It has been reviewed by expert medical and health professionals and people living with cancer. It has been approved by Chief Medical Editor, Professor Tim Iveson, Consultant Medical Oncologist.

    Our cancer information has been awarded the PIF TICK. Created by the Patient Information Forum, this quality mark shows we meet PIF’s 10 criteria for trustworthy health information.

Date reviewed

Reviewed: 01 December 2022
Next review: 01 December 2025
Trusted Information Creator - Patient Information Forum
Trusted Information Creator - Patient Information Forum

Our cancer information meets the PIF TICK quality mark.

This means it is easy to use, up-to-date and based on the latest evidence. Learn more about how we produce our information.