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Introduction: Breast carcinoma is the most common invasive cancer in female gender. Neoadjuvant Chemotherapy (NAC) helps to achieve resectability. The pathological response to NAC is classified as a pathological Complete Response (pCR), pathological Partial Response (pPR) and pathological No Response (pNR). Aim: To evaluate the role of Ki-67 as a predictive marker of pathological response and to find the optimum percentage of Ki-67 positivity that can be associated with pCR. Materials and Methods: The present cross-sectional study was conducted in the Department of Pathology, Government Medical College Thrissur, Kerala, India, between March 2021 and January 2022, which involved 50 breast carcinoma patients. Fifty patients who had undergone mastectomy post-NAC were selected. Ki-67 immunohistochemical staining was done on the initial trucut biopsy sample of the patients. Post-NAC mastectomy specimens were evaluated for tumour clearance. Association of Ki-67 score with pathological response in the mastectomy specimen was studied. Percentage cut-off for Ki67 in initial trucut biopsy of breast, that could effectively predict pCR in the post-NAC mastectomy specimens was derived by Receiver Operating Characteristic (ROC) curve analysis. Results: Total 50 cases of breast cancer were studied with mean±Standard Deviation (SD) age of 53.3±10.3 years. Eight (16%) out of 50 patients had achieved pCR while, 18 out of 50 patients (36%) showed pPR and 24 out 50 patients (48%) had pNR. Significant association between Ki-67 score and pathological response (p-value=0.03) was found. Optimal percentage cut-off for Ki-67 that could predict pCR was found to be 40% (p-value=0.023). Conclusion: Ki-67 can be used as an independent predictive marker of pathological response in patients undergoing NAC. Ki67 value of more than 40% shows strong association with pCR.