Circulating tumor cells (CTCs) are tumor cells that shed from primary tumor and circulate in peripheral blood, and can be a useful clinical marker in early diagnosis and monitoring therapeutic effects for patients with malignant tumors. Detection of rare CTCs contaminated among a large number of hematologic cells presents a technical challenge, but recent technological advances in detection methods of CTCs, especially development of an automated detection system (the CellSeach system), have made it possible to isolate and quantitatively evaluate CTCs. Here, we reviewed clinical implications of CTCs in thoracic malignant tumors such as primary lung cancer and malignant pleural mesothelioma (MPM).