When a patient has cancer, a diagnostic workup is performed in order to determine the primary type of cancer. If the doctors know about the primary cancer type, they can choose the most appropriate cancer treatment for the patient. Since metastases originate from the primary cancer, they are often treated the same.1 Therefore, the doctors try as many methods as possible to identify the primary cancer.


The diagnosis of CUP is made when all other primary cancer types have been ruled out by a thorough diagnostic workup – it is a diagnosis by exclusion. This does not mean that the doctors have failed, it is a characteristic of the CUP cancer type.

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Imaging techniques

Different methods may be used for obtaining an insight into the inner body:

  • X-ray uses invisible radiation to create an image of the relevant part of the body.
  • Computed tomography (CT) uses X-rays to produce slice-wise pictures of the inner body.
  • Magnetic resonance imaging (MRI) produces slice-wise pictures of the inner body, but without X-ray radiation.
  • Ultrasound imaging, also called sonography, applies sound waves to create images.
  • Endoscopy uses a small camera to allow a direct visual examination of the inside of a hollow organ or a cavity in the body, e.g., the stomach.
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Laboratory tests on body fluids such as blood, urine, and others can provide information about how well the body’s organs function. Tests checking the presence of specific substances in the blood (so-called biomarkers) may help to identify the suspected origin of cancer.

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During a biopsy, cells or a small part of the tissue to be investigated are removed from the body to be examined by microscopy and …

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… histology: For this the biopsy sample is coloured in the laboratory in a specific way and compared to a coloured sample of normal cells under a microscope. Thereby, differences between normal cells and the biopsy sample may be identified.

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… immunohistochemistry: Here it is tested if specific antibodies can help to identify the exact cancer type by interacting with the biopsy sample.

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Genomic testing tries to identify the genes which may have changed and have thereby contributed to the growth and spread of the cancer. This may lead to further treatment possibilities.


In order to provide guidance for a standard of care for CUP patients, hospitals or countries may have developed their own guidelines for medical staff. Moreover, medical guidelines from international cancer societies are available. Guidelines may include information about biology, diagnosis, treatment and follow-up of the relevant disease. Medical staff is advised to respect these guidelines when treating a patient.
For example, the European Society For Medical Oncology (ESMO) released an international guideline for CUP in 2015.1


  1. Fizazi K et al. Annals of Oncology 2015; 26 Suppl 5: v133–138.


In the course of the diagnostic workup you may have been sent to several different medical experts like oncologists and organ specialists – this is perfectly normal for patients with CUP syndrome. Doctors want to make sure that they have tried their best to identify the primary tumour.


The diagnostic workup may feel extremely exhausting for you. It is important that you trust your medical team and feel comfortable with them. Tell them about your needs, otherwise they don’t know.

“You have to know what's driving your cancer. If you don't know who's driving the bus, you're in trouble. So, what genomic testing does, it allows me to understand what's driving my cancer bus.” – Don, cancer survivor


Talk to your doctor about diagnostic options.