Cancers of unknown primary site (CUPs) represent a heterogeneous group of metastatic tumors for which a standardized diagnostic work-up fails to identify the site of origin at the time of diagnosis. CUPs account for 3–5% of all malignancies. The unique biology of these tumors remains unknown. Nonetheless, current data suggest that metastatic dissemination can occur in the absence of growth of a primary tumor by virtue of inherent metastatic aggressiveness of cancer cells or through site-specific transformation of circulating cells, by oncogene induction at metastatic stroma.
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