Publisher Summary This chapter discusses the methodology of circulating cancer cells (CCC). All small amounts of cancer cells discovered anywhere except in a primary or metastatic lesion are called CCC. There are three patterns for cancer metastasis: the blood circulation pattern, the lymph-node pattern, and the abdominal-dissemination pattern. These sites are targeted to find recurrence or metastasis for the postoperative imaging investigation. The investigation for isolated tumor cells (ITC) or CCC is mainly focused on peripheral blood (PB), lymph nodes, ascites, and bone marrow (BM). The shedding of cancer cells, from either primary tumors or lymphatic organs, into the circulating blood, is a result of primary dissemination. Patients without metastasized regional lymph nodes tend to do far better than patients with lymph-node metastasis. The investigation of cancer cells in BM proves to be a pertinent diagnostic technique when identifying metastasis. Metastasis in ascites provides information that can change the operative procedure. Immunohistochemical methods are based on the ability of monoclonal or polyclonal antibodies to distinguish specific histogenesis cells among others. A real-time quantitative polymerase chain reaction (RT-PCR) is used to develop a highly sensitive diagnostic device that could detect ITC and CCC in BM and PB.