Introduction Worldwide, breast cancer is still the most common cancer that affects women. Breastcancer prognosis is based on a number of clinical and pathological indicators. Further features are needed to predict early metastasis andprognosis of patients with breast carcinoma, as the current pathological characteristics, such as tumor differentiation, vascular infiltration, and TNM (tumor, node, and metastasis) staging, cannot fully describe the early metastatic biological behavior in breast carcinoma. High Ki-67 expression is seen to be associated with worse survival in cancer patients. Hence, this study was conducted to study the utility of Ki-67as a prognostic marker in invasive breast carcinoma and its association with known clinicopathological factors. Methodology The study was a hospital-based cross-sectional study carried out in the Histopathology Section of the Department of Pathology, Shri BM Patil Medical CollegeHospital and Research Centre, Bijapur Lingayat District Education (BLDE) (Deemed to be University), Vijayapura. The study was conducted between September 1, 2022, and April 30, 2024. The study population consisted of 55 cases of mastectomy specimens of primary breast cancer admitted to our hospital. Data regarding the patient's age, tumor size, histological type, histological grade, lymph node status, and vascular invasion were noted from medical records. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu (HER2/neu) proto-oncogene, and Ki-67 markers was performed according to standard protocol. The relationship of Ki-67with these clinicopathological parameters was analyzed statistically. Results In the current study, high-grade Ki-67 nuclear positivity was seen in 30 cases out of 55 cases, and low-grade Ki-67 was seen in the remaining 25 cases. The association of Ki-67 with tumor size and histological grade showed statistical significancewith a p-value of less than 0.05 and 0.001, respectively. However, no statistical significance was seen with lymph node status, vascular invasion, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu)proto-oncogene status with p-values greater than 0.05. Conclusion The expression of Ki-67 was statistically significant with histological grading and tumor size in our study. Immunohistochemical determination of the Ki-67 proliferation index should be performed in routine cases of breast cancerto obtain clinically useful information on tumor aggressiveness as reflected in their proliferative rate. Hence, Ki-67 can be used as a predictive and prognostic marker in managing breast cancer patients.