Abstract
OBJECTIVE: In this article, we review the role of imaging in cancer of unknown primary site (CUP) diagnosis and management and the utility of immunohistochemistry, serum tumor markers, and molecular profiling in the optimized care of CUP patients. CONCLUSION: With advances in imaging, pathology, and molecular medicine, the diagnosis and management of CUP have evolved into more personalized and site-specific therapies. A multidisciplinary integrated approach among oncologists, pathologists, and radiologists is extremely important.