Circulating tumor cells (CTCs) in patients with breast cancer can be regarded as the pre-stadium of clinically manifest distant metastases. Here we present results on CTCs determination in peripheral blood (PB) of breast cancer patients in the context of treatment. Ninety-two patients were enrolled onto a prospective, unicenter study and 71 of those subjects are the focus of our analyses. CTC assessment was performed by isolating cytokeratin-positive (CK) cells by immunomagnetic techniques, with further identification by immunocytochemical methods. CTCs were detected in 47 (66%) patients: 35 with primary breast cancer and 12 with metastatic disease. Five (14.3%) of those patients with primary cancer and CTCs showed first disease progression or died. Of those patients with metastatic disease and CTCs before chemotherapy, eleven (91.6%) died. During chemotherapy, >6 CTCs was correlated with a worse prognostic of disease in patients with metastatic disease (p = 0.05). Four weeks after chemotherapy, 59 patients underwent a follow-up assessment. CTCs were detected in 54.2% of those patients. CTCs levels, and not the presence of CTCs alone, was associated with progression free of disease (p = 0.052) and showed borderline significance with overall survival (p = 0.071). The differential prognostic and overall survival showed between patients with and without elevated CTCs before and at the end of chemotherapy, is of special interest in patients without clinical evidence of metastasis.