Testing for circulating tumor cells has emerged as a new and promising tool for stratifying and monitoring patients with metastatic disease. Appropriate risk and biologic stratification in breast cancer is important for the development of more effectively tailored targeted therapies. To optimize patient care, it is important for the clinicians to rely on validated and robust tools able to provide accurate predictive and prognostic information for each patient at any time during treatment. The recent demonstration that the presence of circulating tumor cells predicts the prognosis at any time during the treatment of patients with metastatic breast cancer raises the possibility that this approach will allow for a true 'biologic staging' of the disease. Important questions regarding the biological characteristics of cells and the reasons for the reduced capacity of systemic treatments to arrest or eradicate the cancer were raised. A further study suggests that comprehensive analysis of circulating tumor cells is likely to provide new insights into the biology of breast cancer and contribute to defining novel treatments and better prediction of clinical benefit. Efforts are being made to genotype and phenotype micrometastatic cells. Considerable progress has been already accomplished which should lead to further noninvasive, real-time monitoring of these rare events in the adjuvant and metastatic settings.