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How is cancer of unknown primary diagnosed?

Before CUP is diagnosed, you will usually see your GP, who will ask about your symptoms and medical history, examine you, send you for tests and refer you to a specialist doctor.

The specialist will arrange extra tests to work out whether you have primary or secondary cancer. If the tests show that the cancer is secondary, more tests will be done to try to find the primary cancer. The tests you have depend on your health and symptoms, the location of the secondary cancer and the suspected location of the primary cancer.

If the tests find where the cancer started, the cancer is no longer an unknown primary. It will then be treated like the primary cancer type. For example, bowel cancer that has spread to the liver will be given the treatment for advanced bowel cancer.

Tests used to find where the cancer started

  • blood and urine tests – samples of your blood and urine are sent to a laboratory to be checked for abnormal cells and chemicals called tumour markers
  • biopsy – a tissue sample is taken from a tumour, enlarged lymph node or bone marrow and sent to a laboratory for examination; tests on the sample can suggest the primary site
  • endoscopy – uses an instrument to look inside the body and take small tissue samples
  • imaging tests – x-rays, ultrasounds and other scans create images of the inside of the body; PET–CT scans have been shown to help find the primary site in new cases of CUP

A full blood count is a test that checks the levels of red blood cells, white blood cells and platelets. Blood tests can also show how well the kidneys and liver are working. Urine may be tested to look for any abnormal cells or bleeding that may be coming from the bladder or kidneys.

Tumour markers

In some cases, blood, urine or tissue samples may be tested for tumour markers. These are proteins made by some cancer cells. High levels of tumour markers may suggest cancer. However, other conditions can also raise the levels of tumour markers, and some people with cancer have normal levels. Tumour marker levels can’t be used on their own to diagnose the primary cancer, but they may suggest certain types of cancer for your doctors to look for.

A biopsy is when doctors remove a sample of cells or tissue from an area of the body. A specialist doctor called a pathologist examines the sample under a microscope to look for signs of cancer and work out what type of cell is affected. This can point to where in the body the cancer may have started.

For a biopsy, you will usually have a local anaesthetic to numb the area. In some cases, you may need a general anaesthetic, which puts you to sleep.

Ways of taking biopsies

There are different ways of taking a biopsy and you may need more than one type. A biopsy is often done using an ultrasound or CT scan to guide the needle to the correct place. You might not have a biopsy if the cancer is too hard to reach or if you are too unwell for the procedure.

Common types of biopsies used to diagnose cancer include:

  • fine needle aspiration – removes cells using a thin needle
  • core biopsy – removes tissue using a hollow needle
  • incision biopsy – cuts out part of a tumour
  • excision biopsy – cuts out the whole tumour.

Tests on the biopsy sample

Using special stains (immunohistochemistry) – After the biopsy procedure, the sample will be sent to a laboratory, where a pathologist uses a series of stains on the sample. These stains may show changes in the cells or highlight markers (e.g. specific proteins) that are linked to certain types of cancer.

Looking at the molecular level – In some cases, you may be offered extra tests on the biopsy sample. These are called molecular or genomic tests, and they look for gene changes and other features in the cancer cells that may be causing them to multiply and grow. The results may suggest what the primary cancer is most likely to be and which targeted therapy drugs may work best to treat it.

Molecular testing for CUP is not covered by Medicare, which can make it expensive. Check what costs are involved and how helpful it would be. If you are having molecular testing as part of a clinical trial, the costs may be covered. Ask your cancer specialists for more information about these  specialised tests.

This procedure is used to look inside the body for any abnormal areas. It is done with an endoscope – a thin, flexible tube with a light and camera on the end. The endoscope is put into the body through a natural opening (such as the mouth) or a small cut made by the surgeon. The camera projects images onto a monitor so the doctor can see inside the body. If they see something suspicious, they can also take a tissue sample (biopsy) using the endoscope.

Common types of endoscopy

  • bronchoscopy or endobronchial ultrasound (EBUS) – checks the lungs or respiratory tract (airways); tube inserted through the mouth or nose.
  • colonoscopy – checks the colon (large bowel); tube inserted through the anus.
  • colposcopy – checks the vagina and cervix; placed outside the vulva and vagina, held open by a speculum.
  • cystoscopy – checks the bladder; tube inserted through the urethra.
  • gastroscopy – checks the oesophagus, stomach and first part of the small bowel; tube inserted through the mouth.
  • hysteroscopy – checks the uterus (womb); tube inserted through the vagina.
  • laparoscopy – checks the abdominal cavity, liver, bowel, uterus and ovaries; tube inserted through small cuts in the abdomen.
  • laryngoscopy – checks the larynx (voice box); tube inserted through the mouth.
  • sigmoidoscopy – checks the lower part of the colon (large bowel); tube inserted through the anus.
  • thoracoscopy – checks the lungs; tube inserted through a small cut in the chest.

These scans create images of the inside of your body and provide different types of information. Your doctors will recommend the most useful scans for your situation. Ask your doctor or imaging centre what you will have to pay and whether Medicare covers the cost.

Before having scans, tell the doctor if you have any allergies or have had a reaction to dyes during previous scans. You should also let them know if you have diabetes or kidney disease, or are pregnant or breastfeeding.


  • How it works – uses low-energy beams of radiation to create images of parts of the body, such as bones and the chest
  • How long does it take – 10-30 minutes
  • What happens – you hold still in front of or on a machine while the images are taken; you might be injected with a dye (contrast) to improve the  image
  • Special notes – painless; the small dose of radiation will not make you give off radiation


  • How it works – uses a low-dose x-ray to create an image of the inside of the breast
  • How long does it take – 10-30 minutes
  • What happens – your breast is placed between 2 x-ray plates, which press together firmly to spread the breast tissue
  • Special notes – can be uncomfortable


  • How it works – uses soundwaves that echo when they meet something solid, such as an organ or tumour; a computer turns the soundwaves into a picture of the inside of the body
  • How long does it take – 10-20 minutes
  • What happens – a cool gel is spread on your skin and a handheld device called a transducer sends out the soundwaves as it is moved across the area; some transducers are wands that can be inserted in a body cavity
  • Special notes – usually painless, but can be uncomfortable

CT scan (computerised tomography scan)

  • How it works – uses x-ray beams and a computer to create detailed pictures of the inside of the body; the scanner is large and round like a doughnut
  • How long does it take – up to 30 minutes
  • What happens – before the scan, you may be given a drink or injected with a dye (contrast) to make the pictures clearer; you lie still on a table that moves in and out of the scanner
  • Special notes – painless; the dye may make you feel hot all over and leave a bitter taste in your mouth

PET–CT scan (positron emission tomography scan with CT scan)

  • How it works – uses a low-dose radioactive solution to measure cell activity in different parts of the body; when combined with a CT scan it provides more detailed information about the cancer
  • How long does it take – about 2 hours
  • What happens – you are injected in the arm with a small amount of radioactive solution, wait 30–90 minutes for it to move through your body, and then have the scan; cancer cells take up more of the solution than normal cells do and light up on the scan
  • Special notes – the solution leaves your body in urine after a few hours; you may be told to avoid children and pregnant women for a number of hours

Bone scan

  • How it works – uses radioactive dye to show any abnormal bone growth
  • How long does it take – several hours
  • What happens – you are injected in the arm with a small amount of radioactive dye, wait 2–3 hours for it to move through your bloodstream to the bones, then your body is scanned; a larger amount of dye will usually show up in any areas of bone with cancer cells
  • Special notes – the dye leaves your body in urine after a few hours; you may be told to avoid children and pregnant women for a number of hours

MRI scan (magnetic resonance imaging scan) 

  • How it works – uses a magnet and radio waves to build up detailed pictures of an area of the body
  • How long does it take – 30-90 minutes
  • What happens – dye (contrast) may be injected into a vein to make the images clearer; you lie on a table that slides into a narrow metal cylinder that is open at both ends; the scan is noisy, so you will often be given earplugs or headphones
  • Special notes – let the medical team know if you feel anxious, you may be given medicine to help you relax; people with some pacemakers or other metallic objects cannot have an MRI

Featured resources

Cancer of Unknown Primary - Your guide to best cancer care

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This information is reviewed by

This information was last updated September 2022 by the following expert content reviewers: Prof Chris Karapetis, Network Clinical Director (Cancer Services), Southern Adelaide Local Health Network, Head, Department of Medical Oncology, and Director, Clinical Research in Medical Oncology, Flinders Medical Centre and Flinders University, SA; Dr Amey Aurangabadkar, Radiologist, Illawarra Radiology Group, NSW; Clare Brophy, Consumer; Prof Katherine Clark, Clinical Director of Palliative Care, NSLHD Supportive and Palliative Care Network, Northern Sydney Cancer Centre, Royal North Shore Hospital, NSW; Prof Wendy Cooper, Senior Staff Specialist, Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, NSW; A/Prof Richard Gallagher, Head and Neck Surgeon, Director of Cancer Services and Head and Neck Cancer Services, St Vincent’s Health Network, NSW; Dr Chloe Georgiou, Oncology Research Fellow, Australian Rare Cancer Portal, and Oncology Trials Fellow, Bendigo Health Cancer Centre, VIC; Dr Susan Harden, Radiation Oncologist, Peter MacCallum Cancer Centre, VIC; Justin Hargreaves, Medical Oncology Nurse Practitioner, Bendigo Health Cancer Centre, VIC; Dr Laura Kirsten, Principal Clinical Psychologist, Nepean Cancer Care Centre, NSW; Prof Linda Mileshkin, Medical Oncologist, Peter MacCallum Cancer Centre, VIC; Caitriona Nienaber, 13 11 20 Consultant, Cancer Council WA.