Today, sentinel lymph node biopsy (SLNB) is considered the gold standard for axillary staging in early breast cancer patients with clinically negative lymph nodes (cN0). SLNB allows to determine the axillary lymph node status sparing the axillary dissection (AD) and its potential complications (seroma formation, loss of sensation, shoulder dysfunction and lymphedema). On the other hand, SLNB for nodal staging in breast cancer patients with clinically negative lymph nodes after neoadjuvant chemotherapy (ycN0) is a highly debated topic due to different reported success rates. In order to optimize oncological results, high identification rate (> 90%) and false negative rate as low as possible (< 10%) should always be obtained when performing SLNB after neoadjuvant chemotherapy. The success rates of SLNB after neoadjuvant chemotherapy (NAC) mainly depend on the clinical lymph node status pre-NAC. In patients with pre-NAC clinically negative nodes (cN0) and at restaging with post-NAC clinically negative nodes (ycN0), SLNB after chemotherapy should be performed because it is an accurate and safe procedure. In patients with pre-NAC clinically positive nodes (cN+) and at restaging with post-NAC clinically negative nodes (ycN0), SLNB after chemotherapy might be considered thanks to the high lymph nodal pathologic complete response rate; however, in this last setting, individual ability, technical skills and repetitive performance of specific tasks must always be followed to improve the identification rate and false negative rate. AD may be avoided only if sentinel lymph node is negative [ypN0(sn)]; instead, to date, patients with metastatic sentinel lymph node after neoadjuvant chemotherapy, even with only isolated tumor cells, [ypN+(sn) including ypN0i+(sn) and ypN1mic(sn)] should always be treated with AD. However, NAC significantly increases the difficulties and complexity of axillary surgical management. A personalized multidisciplinary path in specialized breast centers should ensure an accurate clinical counselling and refined patient selection for SLNB post-NAC.