Carcinoma of Unknown Primary (CUP) is defined as a heterogeneous group of tumors with unique biological characteristics. Adenocarcinoma is the most common pathology type. CUP is the 6th to 8th most common cancers worldwide, accounting for 2.3%-5.0% of all tumors, and the 3rd to 4th most common cause of death from cancer. The primary site of CUP is difficult to detect. The diagnostic methods include physical examination, laboratory and imaging examination, endoscopies, immunohistochemistry (IHC) and gene expression profiling techniques (GEP). Pathology and IHC are the gold standard of diagnosis. The incidence of CUP has decreased in recent years with the development of diagnostic techniques. The prognosis of CUP patients are affected by various factors, such as the primary site, metastases and number, pathological type, treatment, physical status, and LDH. Due to its unique biological characteristics, the clinical trials are difficult to develop, and the overall prognosis of CUP patients is poor.15%-20% of CUP patients have a good prognosis, 80%-85% have a poor prognosis and the median survival is less than 1 year. Traditional empirical treatments include platinum or paclitaxel-based chemotherapy, radiation therapy, and surgery. It does not improve the prognosis of CUP patients. Molecular diagnostic techniques such as GEP can identify the molecular characteristics of CUP patients. Molecular profiling provides a practical and useful complement to histomorphology, making targeted therapy possible and opening up a new approach therapy of CUP. The specific therapy, targeted therapy and immunotherapy under the guidance of molecular diagnosis are expected to make the treatment individualized and precise, which is conducive to improving the quality of life and survival of patients. The diagnosis and therapy of CUP are still controversial at present. This article reviews the common diagnostic methods and treatment of CUP.
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