Sentinel lymph node (SLN) biopsy has been shown to predict axillary metastases accurately in early stage breast cancer. Some patients with locally advanced breast cancer receive preoperative (neoadjuvant) chemotherapy, which may alter lymphatic drainage and lymph node structure. In this study, we examined the feasibility and accuracy of SLN mapping in these patients and whether serial sectioning and keratin immunohistochemical (IHC) staining would improve the identification of metastases in lymph nodes with chemotherapy-induced changes. Thirty-eight patients with stage II or III breast cancer treated with neoadjuvant chemotherapy were included. In all patients, SLN biopsy was attempted, and immediately afterward, axillary lymph node dissection was performed. If the result of the SLN biopsy was negative on initial hematoxylin and eosin-stained sections, all axillary nodes were examined with three additional hematoxylin and eosin sections and one keratin IHC stain. SLNs were identified in 31 (82%) of 38 patients. The SLN accurately predicted axillary status in 28 (90%) of 31 patients (three false negatives). On examination of the original hematoxylin and eosin-stained sections, 20 patients were found to have tumor-free SLNs. With the additional sections, 4 (20%) of these 20 patients were found to have occult lymph node metastases. These metastatic foci were seen on the hematoxylin and eosin staining and keratin IHC staining. Our findings indicate that lymph node mapping in patients with breast cancer treated with neoadjuvant chemotherapy can identify the SLN, and SLN biopsy in this group accurately predicts axillary nodal status in most patients. Furthermore, serial sectioning and IHC staining aid in the identification of occult micrometastases in lymph nodes with chemotherapy-induced changes.