Circulating tumor cells (CTC) can be identified and characterized in blood of patients with many solid tumors, particularly breast cancer. Between 10% and 30% of patients with stage I to III breast cancer and 50% to 70% of women with metastatic breast cancer have detectable CTCs. In both cases, presence and elevation of CTCs are associated with worse prognosis. In the metastatic setting, persistent CTC after 3 to 5 weeks of a new therapy seem to indicate lack of activity of that regimen, and an ongoing prospective randomized clinical trial is addressing the relative worth of changing to an alternative treatment rather than waiting for classic clinical and radiologic evidence of progression. Recent technical advances offer the promise of further genotyping and phenotyping for important tumor-associated genes and proteins.