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Carcinomas of unknown primary origin (CUP) are histologically confirmed metastatic malignancies with no identifiable primary tumor, which account for 3–5% of all malignancies. Having a specific and unique phenotype of early and usually aggressive metastatic dissemination with no identifiable primary tumor, CUP is clinically challenging for physicians. The diagnostic workup of patients suspected of having malignant disease includes a careful clinical and extensive histopathological examination, as well as the use of adequate imaging techniques.

The diagnosis and treatment of patients with CUP first requires recognition of the biological properties of CUP. Secondly, CUP can be divided into favorable and unfavorable subsets. We must pick out favorable subsets of patients with curable potential. Thirdly, treatment that is specific to the suspected type of cancer is likely to be more effective, so when diagnostic tests have not identified the primary site, the potential benefits of more extensive testing must be weighed against patient discomfort and financial costs. Finally, although most patients with CUP do not confirm to any previously defined curable or favorable subset, standard therapy for patients in the unfavorable CUP subset who have a good performance status is a platinum-based doublet chemotherapy, although an optimal chemotherapy regimen for these patients remains to be determined.

The emergence of robust immunohistochemical staining techniques and the growing field of molecular profiling has increased the need for tailored approaches to patient management. Improvements in care for patients with CUP need the conduct of randomized clinical trials with national and international cooperation. In this session, I outline the clinical evaluation of patients with CUP and discuss the latest treatment strategies and outcomes of these patients.

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