Cancer of unknown primary site: 20 questions to be answered.

Cancer of unknown primary (CUP) is a common, well-recognized and heterogeneous clinical syndrome. Patients with CUP present with metastatic disease in the absence of an identifiable primary tumour despite a diagnostic work-up. Aetiologically, CUP might either harbor primaries that cannot be detected by the standardized diagnostic investigations or carry distinct genetic and epigenetic aberrations. In this article we try to clarify the clinical and pathological enigma of CUP by answering 20 important questions related to this entity.