Tests for cancer of unknown primary (CUP)

Cancer of unknown primary (CUP) means that there are cancer cells in your body but your doctors don’t know where the cancer started. The tests you have to help diagnose CUP depend on your symptoms and where in your body the cancer is.

You may hear doctors using the terms primary and secondary cancer. A primary cancer is the place where a cancer starts growing. Cells from the primary cancer may break away and spread to other parts of the body. These escaped cells can grow and form other tumours which are known as secondary cancers or metastases.

You have a number of tests to try to find out the cause of your symptoms. If tests show that you have secondary cancer, then you usually have more tests to try to find out where the cancer started. You have a confirmed cancer of unknown primary (cCUP) if doctors can’t find the primary cancer after having the tests. 

Sometimes doctors find the primary cancer at a later date. When this happens, the cancer is no longer a CUP and your treatment will follow the guidelines for the specific cancer type.

Tests you might have to find out the cause of your symptoms

Most people are diagnosed with CUP after they become unwell and go to A&E. Others start by seeing their GP if they have symptoms that could be due to cancer. Some people are also diagnosed after having tests for something else.

If you see your GP, they might do some tests to help them decide if you need to see a specialist. The tests they might do include:

  • a physical examination

  • blood tests

  • an x-ray

Your GP may also arrange for you to have other tests such as an MRI or CT scan. This depends on your symptoms and test results.

Physical examination

Your doctor feels for any areas that are swollen or might not feel normal. If you have any pain they will feel those areas. It might feel tender, or it might be possible to feel a lump.

They may also listen to your chest and tummy (abdomen) to find out if they sound normal.

Blood tests

Blood tests can check your general health including:

  • how well your liver and kidneys are working
  • the number of blood cells in your blood such as white blood cells, Open a glossary item platelets Open a glossary item and red blood cells. You may hear this being called a full blood count Open a glossary item
  • if you have any signs of infection


X-rays use high energy rays to take pictures of the inside of your body. They are a good way to look at changes in organs, such as the lungs.

You may have an x-ray to help find the cause of your symptoms. For example, you might have a chest x-ray if you are having problems with your breathing. 

You have an x-ray in the imaging department of your local hospital.

Which specialist will I see?

Your GP looks at your symptoms and test results. They might then refer you to a specialist. For example, they may refer you to:

  • a gastroenterologist if you have bowel or stomach problems

  • a lung specialist if you have problems with your breathing

  • a urologist if you have problems passing urine

  • an ear, nose and throat (ENT) doctor if you have a lump in your neck

Your specialist usually does more tests. These might include:

  • taking a sample of tissue called a biopsy

  • CT scan

  • MRI scan

  • ultrasound scan

  • PET-CT scan

  • tumour marker tests

Your doctor decides what tests to do depending on where the secondary cancer is in your body.

We haven’t listed all the tests you might have. We have more information about tests to diagnose cancer in our general cancer test section.


A biopsy means taking a sample of tissue so that it can be looked at under a microscope. This is the only way to find out if an abnormal area is cancer or not. Your doctor takes a sample of the abnormal area and sends the sample to the laboratory. This is where a doctor called a pathologist Open a glossary item looks at it under a microscope and checks for cancer cells.

There are different ways to have a biopsy. The type of biopsy you have depends on where in your body the abnormal area is.

CT scan

A CT (or CAT) scan stands for computer (axial) tomography. It is a test that uses x-rays and a computer to create detailed pictures of the inside of your body. The computer puts them together to make a 3 dimensional (3D) image.

You usually have a CT scan of your chest, abdomen and pelvis.

MRI scan

MRI stands for magnetic resonance imaging. It uses magnetism and radio waves to take pictures of the inside of the body.

You might have an MRI scan to look for where the cancer started. For example, you might have an MRI scan of the breast if your doctor thinks the cancer started in the breast.

Ultrasound scan

Ultrasound scans use high frequency sound waves to create a picture of a part of the body. The ultrasound scanner has a probe that gives off sound waves. The probe looks a bit like a microphone. The sound waves bounce off the organs inside your body, and the probe picks them up. The probe links to a computer that turns the sound waves into a picture on the screen.

You might have an ultrasound scan to look at organs in your abdomen and pelvis, such as the liver or testicles. Or you may have it to check the lymph nodes Open a glossary item in your neck. The type of ultrasound scan you have depends on your symptoms.

PET-CT scan

A PET-CT scan combines a CT scan with a PET scan. It gives detailed information about your cancer.

You have a PET-CT scan in the radiology department. It usually takes between 30 to 60 minutes. A PET-CT scan can help to show a cancer that other scans have not been able to find. 

You may have a PET-CT scan of your head and neck if doctors find cancer cells in the lymph nodes of your neck.

Tumour marker tests

Tumour markers are substances that can be raised if there is a cancer. They are usually proteins that are in the blood, urine or body tissues.

Some tumour markers are only produced by one type of cancer. Others can be made by several types. Some markers are also raised in other medical conditions.

Tumour markers your doctor might test for include:

  • Human chorionic gonadotrophin (HCG) and alpha feto protein (AFP). These can be raised in people with germ cell tumours Open a glossary item, such as testicular cancer or a type of ovarian cancer
  • AFP which can be raised with primary liver cancer
  • Prostate specific antigen (PSA) in men. A raised PSA level can suggest that a cancer of unknown primary may have started in the prostate
  • CA125 which can be raised in some women with ovarian cancer
  • CEA can be raised in a number of different cancers such as bowel or pancreatic cancer
  • CA 19-9 is sometimes raised in people with pancreatic cancer

Your doctor may use tumour markers to monitor how well your treatment is working or check if the cancer has come back.

Tests in your cancer cells

Your doctor might do further tests on the tissue sample used to diagnose CUP. They might do tests that look for particular proteins on the surface of the cancer cells. These are called immunohistochemistry (IHC) tests. IHC tests can sometimes tell which type of cell the cancer started in.

Looking at genes or molecules in the cancer tissue

Techniques called gene expression profiling and molecular profiling are available for research purposes. But they are not routinely available on the NHS. Researchers need to find out more about how these tests can help to diagnose CUP.

Some clinical trials are looking at molecular profiling for people diagnosed with CUP. Your doctor might suggest you enter a trial if one is available.

When doctors stop looking for the primary cancer

It may not be helpful to spend time doing further tests to try to find where the cancer started. So your team might suggest starting treatment straight away to help control your symptoms.

Doctors might stop looking for the primary cancer when:

  • the results of further tests are unlikely to change your treatment

  • you are not well enough to have treatment

If doctors find the primary cancer at a later date, your cancer is no longer a CUP. Your treatment might change so it follows the guidelines for the specific cancer.

We haven’t listed all the tests you might have here. We have more information about the tests to diagnose cancer in our general cancer tests section.


All the tests give your doctor some information about the type of cancer you have. This helps them decide on the best treatment for you.


It can be very shocking to be told that you have cancer that has spread. Not knowing where the cancer started can make the news even harder to take in. Your treatment team, including your specialist nurse, will do all they can to support you and your family.

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  • Routes to Diagnosis, 2018
    NHS Digital, 2022

  • Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
    Annals of Oncology, 2023. Vol 34, Issue 3, Pages 228-246.
    A Krämer and others

  • Cancer: Principles and Practice of Oncology (12th edition)
    VT DeVita, TS Lawrence, SA Rosenberg
    Wolters Kluwer, 2023

  • The Royal Marsden Manual of Clinical and Cancer Nursing Procedures (10th edition, online)
    S Lister, J Hofland and H Grafton 
    Wiley Blackwell, 2020

  • The information on this page is based on literature searches and specialist checking. We used many references and there are too many to list here. Please contact patientinformation@cancer.org.uk with details of the particular issue you are interested in if you need additional references for this information.

Last reviewed: 
16 May 2024
Next review due: 
16 May 2027

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