What is cancer of unknown primary?

Cancer of unknown primary (CUP) means that cancer spread (secondary cancer) has been found in your body, but doctors don't know where the cancer started (the primary cancer).

Your body is made up of billions of cells that can only be seen under a microscope. The cells group together to make up the tissues and organs of our bodies.

Normally, cells only divide to replace old and worn out cells. Cancer develops when something inside a single cell goes wrong, making the cell carry on dividing until it forms a lump or a tumour.

A tumour can be either non cancerous (benign) or cancerous (malignant). A benign tumour does not spread to other parts of the body. But a malignant tumour (cancer) can spread.

What is a primary cancer?

The primary cancer is the place where a cancer starts growing. Cells from this primary site may break away and spread to other parts of the body through the bloodstream or lymphatic system. These escaped cells can then grow and form other tumours, which are known as secondary cancers or metastases.

Doctors name and treat cancers according to where they first started developing, even if they have spread to other parts of the body.

For example, if you have bowel cancer that has spread to the liver, it is called bowel cancer with liver metastases or secondaries. It is not called liver cancer. This is because the cancerous cells in the liver are cancerous bowel cells. They are not liver cells that have become cancerous. Doctors confirm this by looking at the cells under the microscope.

Diagram showing a primary and secondary cancer

Looking for the primary cancer

It's normally straightforward to find the primary cancer. Usually, people go to their GP because of symptoms. The GP might then refer you to a specialist doctor and for tests that confirm where the cancer started (the primary tumour).

Sometimes secondary cancers are found in one or more parts of the body, but despite several tests, doctors can't find the primary tumour. If tests show that you have a cancer that has spread, but your doctors can’t find the primary tumour, it’s called a malignancy of unknown primary origin (MUO). 

You then have some initial tests to try to find out the primary cancer. If the primary cancer doesn’t show up on the initial tests, your doctor may refer you to a team of doctors who specialise in cancer of unknown primary (CUP).

The CUP specialist team may arrange for more tests to search for the primary cancer. You have a confirmed cancer of unknown primary (cCUP) if they can't find the primary cancer after the specialised tests.

Why a primary cancer might not be found

There are different reasons why doctors can't find a primary cancer. They don’t always know for certain why and how this happens. This might be because:

  • the secondary cancer has grown very quickly, while the primary cancer is still very small – very small cancers might not cause symptoms or be seen on scans

  • your immune system has successfully attacked the original primary cancer and it has disappeared, while the secondary cancer is still growing (this is not common, but it can happen)

The most common places for secondary cancers to be found are the lungs, liver, bones, lymph nodes, and skin.

How doctors know you have CUP

Doctors can often tell the type of cancer by what the cells look like under a microscope. For instance, cells taken from a tumour in the lung might look like breast cancer cells. So the doctor knows it is breast cancer that has spread to the lung, rather than a cancer that started in the lung. 

Sometimes cancer cells don’t look like any particular type of normal cell. The cells are very abnormal and have not become specialised enough to look like breast cells or lung cells, for example. Cells like this are known as poorly differentiated or undifferentiated.

This can make it very difficult for the doctor to tell what kind of cell the cancer started from.

Types of cells and cancer

Most cancers are cancers of the epithelial cells. Epithelial cells are found in the skin or tissues that line or cover the internal organs. Cancers that start in epithelial tissue are called carcinomas. Most cancers of unknown primary are types of carcinoma.

Other types of cancer develop from different types of body cell. They include:

  • sarcomas, which develop from cells of the connective and supportive tissue, such as bones, muscle, fat, blood vessels or other soft tissues
  • leukaemias, which are cancers of white blood cells found in the bone marrow
  • lymphomas, which are cancers that begin in cells of the immune system

How common is cancer of unknown primary (CUP)?

Around 8,600 people are diagnosed with cancer of unknown primary in the UK each year. That's about 2 out of every 100 cancers diagnosed (2%). 

Who gets it?

Cancer of unknown primary can develop at any age. But almost 60 out of 100 cases (almost 60%) are in people over the age of 75.

Symptoms of CUP

Symptoms of CUP depend on where the cancer has spread to in your body. Possible symptoms of CUP include:

  • weight loss

  • sickness and loss of appetite

  • weakness or feeling very tired

  • pain

  • breathlessness

  • a cough that won't go away

  • swollen lymph nodes

These symptoms listed here are more often caused by other medical conditions. But if you have any of them it is important to see your doctor.

  • Cancer Incidence from Cancer Intelligence Statistical Information Team at Cancer Research UK  (2016 - 2018 UK average) 
    Accessed May 2024

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

  • 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

  • Metastatic malignant disease of unknown primary origin in adults: diagnosis and management
    National Institute for Health and Care Excellence (NICE), 2010 (updated April 2023)

  • Adenocarcinoma of unknown primary
    BMJ Best Practice, Last accessed May 2024

  • 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: 
13 May 2024
Next review due: 
13 May 2027

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