Introduction.- Epidemiology, risk factors and survival in CUP: pointers to disease mechanisms.- Biologic features of CUP.- Prognostic factors and their role in the management of CUP.- Diagnostic work-up of CUP - an approach to current recommendations and underlying evidence.- The radiologist's approach to CUP.- Cancer of unknown primary: the pathologist's approach.- Treatment of disseminated CUP.- Concepts of radiotherapy in cancer of unknown primary.- Favorable subsets of CUP.- Novel Diagnostic and Therapeutic Strategies in the Management of Patients with Cancers of Unknown Primary Site.- Future directions.