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Cancer of Unknown Primary Diagnosis

With new scientific advances, doctors increasingly are able to find where cancer of unknown primary (CUP) began. In fact, now the primary site can be found in about four of five cases that originally were diagnosed as CUP.

Clues to where CUP began may include where cancer cells are found first, the pattern in which the cells are spreading and the type of cell in the remote cancer.

CUP Diagnostic Tests

The first step in diagnosing CUP is a thorough history and physical examination. The doctor will ask you questions about your current and past health and risk factors, such as smoking or family history.

If your doctor suspects cancer of unknown primary, one or more of the following tests may be done:


Different methods are used to perform biopsies for CUP, depending on where the cancer is and the type of cancer. These include:

Fine needle aspiration (FNA): A thin needle is inserted into the body and cells are drawn out and looked at under a microscope.

Core needle biopsy: Although a slightly larger needle is used, this test is similar to FNA biopsy. It is more common than FNA because it removes a larger piece of tissue, which may give doctors more information.

Excisional biopsy: The entire tumor or swollen lymph node is removed surgically. If the tumor or node is close to the surface of the skin, this procedure can be done in the doctor’s office after the skin has been numbed.

Incisional biopsy: This type of biopsy is similar to an excisional biopsy, but only part of the tumor or lymph node is removed.

Fluid removal: A long, hollow needle is used to remove a small amount of fluid. This is most commonly used if there is a large amount of fluid in the abdomen or lungs.

Bone marrow aspiration and biopsy: A small amount of bone marrow (liquid in the middle of large bones) is withdrawn with a needle that is inserted into the hip bone.

Blood and urine tests

Imaging tests, which may include:

  • X-rays
  • CT or CAT computed axial tomography) scans
  • MRI (magnetic resonance imaging) scans
  • Ultrasound
  • PET (positron emission tomography) scans
  • Endoscopy: An endoscope is inserted into your mouth, nose or anus, depending on where the cancer is. Sometimes the tube is inserted through a small incision (cut) in the skin.
  • Colonoscopy

CUP Staging

Staging is a way of determining how much disease is in the body and where it has spread. This information is important because it determines the type of treatment you will receive and the outlook for your recovery (prognosis). 

CUP Stages

Cancer of unknown primary cannot be staged the way other cancers are because the origin of the primary cancer is not known. But doctors can make some predictions based on:

  • Where the cancer has spread
  • How the cancer cells look under a microscope
  • How well the cancer responds to treatment
  • Your general health

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Knowledge Center

Find the latest news and information about cancer of unknown primary in our Knowledge Center, including blog posts, articles, videos, news releases and more.