Neoadjuvant chemotherapy (NAC) in breast cancer (BC) is being considered for a broader range of cases, including locally advanced tumors and situations where downstaging could reduce extensive surgery. Several trials have explored predictive markers of pathological complete response (pCR). The role of Ki-67 as a predictor of pCR has been demonstrated in studies. However, the cut-off remains vague, given the lack of standardization of measurement methods. The aim of our study was to evaluate the predictive value of Ki-67 in response to NAC and to identify the cut-off values that exhibit the strongest correlation with best response. This retrospective study included 187 patients who had undergone surgery following NAC for BC at the CHU Souss Massa of Agadir between January 2020 and January 2023. Logistic regression was used to assess the correlation between Ki-67 and patients' characteristics. Optimal Ki-67 cutoff was identified by receiver operating characteristic curve. Kaplan-Meier curves were used to assess disease-free survival (DFS), and survival comparisons were assessed with the log-rank test. The median age was 51.8±10.7 years and 51.4% of tumors were smaller than 5 cm. Node invasion was found in 55.4%. Luminal B subtype was found in 49.7%, followed by human epidermal growth factor receptor-2 (HER-2)-positive in 27.4%, triple-negative in 14.3% and Luminal A in 8.6%. pCR occurred in 40% of patients overall. Subgroup analysis revealed a significant association between pCR and tumor size (p<0.001), lymph node involvement (p<0.001), grade 2 (p<0.001), vascular invasion (p<0.001), and positive HER-2 status (p = 0.022). In statistical analysis, pathological responses were improved in patients with Ki-67 >35% (p<0.001). DFS was 98.8% at 12 months. No statistical difference was found in DFS according to Ki-67 values and pCR status. Our results indicate that Ki-67 is a predictive marker for response in the neoadjuvant setting in BC patients. Our study showed that a Ki-67 cut-off >35% predicts a better pCR rate in response to NAC. However, this cutoff value remains controversial due to the absence of a standard method of measurement, with inter- and intra-observer variability. It would be necessary to validate this cutoff in other studies.