Axillary lymph node status at the time of diagnosis is the most important prognostic indicator for women with breast cancer, and may influence management decisions. However, at present its role is controversial, as some groups recommend avoiding axillary lymph node dissection (ALND) in cases with metastasis of any size in the sentinel lymph nodes. Molecular analysis allows full examination of the sentinel lymph nodes in a short time period, discriminatation between macrometastasis, micrometastasis and isolated tumor cells, and helps to predict the performance of ALND. ALND may be the treatment of choice in some patients, even in cases of low-volume metastasis, as chemotherapy does not control regional disease well. In addition, the collection of metastatic cells, as well as the local immune surveillance, is susceptible to further molecular studies that will offer prognostic and predictive information, which may have an impact on therapeutic decisions, so that individualized treatments can be adequately designed.