Aim:The aim of the study was to evaluate the proliferative index (PI) at their invasive front of oral cancer and their association with Bryne's grades of oral squamous cell carcinoma (OSCC) and compare the PI with lymph node metastasis, site of involvement, and habits. Materials and methods:The Ki-67 antigen expression was immunohistochemically evaluated in a total of 102 cases that included the histopathologically diagnosed archival specimens of OSCCs. They were subdivided by Bryne's histopathological grading into grade I (40 cases), grade II (32 cases), and grade III (30 cases). The nucleus with brown stain was considered positive. Cells were counted under 400× magnification. The proliferative activity thus determined was then expressed as a percentage of Ki-67 labeling index (Ki-67 LI) positive cells. Results:A stepwise increase in the mean Ki-67 LI was found from grade I to III squamous cell carcinoma, thus correlating with the histological grading. In addition, there was a higher PI seen in cases associated with metastatic lymph node, which concords with the higher biologic aggressiveness and poor prognosis of the lesion. Conclusion:The present study shows a definitive correlation of Ki-67 antigen with the Bryne's histological grading, all the parameters of Bryne's grading for OSCC and lymph node status of the patient proving its association as an effective tool to grade the tumors and finally read the prognosis of the tumor. Clinical significance: Cell proliferation is regarded as one of the most important biologic mechanisms in oncogenesis. The role of cell proliferation in tumor progression has been inferred in studies concerned with human cancer by comparing the PI of normal tissue, preneoplastic and neoplastic lesions. The Ki-67 antigen-labeled cells can prove to be an effective aid to grade the tumors. It might be possible to standardize and objectify tumor grading among pathology laboratories. Proliferative Index in Invasive Tumor