Approximately 3% to 5% of all human cancers manifest as carcinoma of unknown primary (CUP), which is the seventh most frequent histologically confirmed cancer and the fourth most common cancer-related cause of death in patients of both sexes.1 Currently, CUP evaluation involves standard metastatic workup in combination with immunohistochemical analysis and increasingly sophisticated pathological and genetic analysis. Treatment is targeted at the most likely primary source on the basis of this workup. However, empirical chemotherapy is often used.