© 2016, Society of Surgical Oncology. Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) can be used as an independent prognostic factor in neoadjuvant trials. The objective of this study was to determine the impact of Ki 67 expression and site of response on overall survival (OS) and disease-free survival (DFS) across different molecular subtypes of breast cancer following NAC. Methods: Records from 357 patients who received NAC from 2004 to 2011 were reviewed. Univariate and multivariate analyses were performed to analyze clinical and pathological factors that influence pCR and DFS. Results: Mean follow-up time was 45 months (range 12–112). pCR was achieved in 82 patients (23 %). According to molecular subtypes, rates of pCR were significantly higher for patients with HER2-positive and triple-negative tumors (69.4 and 32.7 %, respectively; p < 0.001) compared with other molecular subtypes. pCR was a predictive factor of longer OS and DFS. The hazard ratio for DFS in patients with positive lymph nodes (ypN1) after NAC was 2.48 (95 % confidence interval 1.47–4.19). Multivariate analysis showed that molecular subtype, changes in Ki 67 expression, and axillary lymph node response were significantly predictors of OS and DFS. Conclusions: pCR in the axilla and posttreatment changes in Ki 67 after NAC are associated with improved survival. Depending on axillary staging before NAC, detection of minimal residual disease—defined as the presence of isolated tumor cells in the SLN after NAC—may confer different prognosis. Further studies are needed to tailor treatments for patients with residual disease after NAC.