Breast cancer is the most frequent type of cancer in women with major cause of death being metastatic disease. Despite aggressive adjuvant systemic therapy with a variety of novel chemotherapeutic and biologic agents recurrence rates vary widely with current conventional prognostic and predictive markers failing to reliably predict recurrence in either node negative (low risk of recurrence) or node positive (considered to have a high risk of recurrence). The ability to detect the presence of minimal residual disease in various body compartments such as the bone marrow, lymph nodes, and peripheral blood represents a viable alternative. Various methods to detect circulating tumor cells (CTCs) have been described including techniques based on polymerase chain reactions (PCR) and cell enrichment methods. Studies have shown that CTCs in metastatic breast cancer can be used as a marker for overall survival and assessment of therapeutic response. The role of CTCs in early stage breast cancer is less well-established. Large prospective trials are needed to further understand its biology and confirm its role as a predictive and prognostic marker before we can incorporate it into the conventional staging system.