Metastasis remains a main cause of death in patients with breast cancer regardless of improvements in treatment. Prospective clinical studies of this minimal residual disease have shown disseminated tumor cells (DTCs) in bone marrow and circulating tumor cells (CTCs) in peripheral blood, neither of which can be detected by conventional imaging, to be prognostic and predictive markers for responsive treatment in patients with metastatic breast cancer. However, the guideline from the American Society of Clinical Oncology does not recommend measuring CTCs for clinical decisions because of a lack of evidence for an established, sound methodology and with proven clinical relevance. The Southwest Oncology Group trial S0500 to validate the clinical relevance of CTCs for treatment decisions in patients with metastatic breast cancer is ongoing. In patients with primary breast cancer, the low detection rate of CTCs has been overcome by recent advances in technology. Although generally DTCs were more detectable than CTCs and the association between presence of DTCs and poor prognosis has been shown, the invasiveness of sample collection of DTCs from bone marrow is generally hard for patients to accept. In this review, we concentrate on the question of whether we need to consider CTCs and DTCs in the management of primary breast cancer on the basis of the evidence of the clinical relevance of CTCs and DTCs. The promising role of the molecular characterization of CTCs, which does have the potential for being a predictor for tumor behavior and development, is suggested as a new targeting strategy.