Despite major advances in breast cancer treatment, the principal cause of death from breast cancer continues to be metastases that are resistant to therapy. Metastasis is a multistep process that requires acquisition of malignant cell phenotypes that allow tumor cells to escape from the primary tumor site. Metastasis is thought to depend in part on adaptation of tumor cells to distant organs. Tumor cells may be shed into circulation in large numbers starting from the early stages of tumor formation. However, only a minority of these dispersed cells produce overt metastases. Circulating tumor cells (CTCs), carcinoma cells detected in the blood of patients with solid tumors, have a Central role in tumor metastasis. The role of CTCs in tumor dissemination can be explained by their relationship to biological processes, including epithelial-mesenchymal transition (EMT). CTCs have established prognostic and predictive value in patients with metastatic breast cancer. However, the prognostic and predictive value of CTCs in nonmetastatic breast cancer is just beginning to be elucidated.