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Introduction: Cyclin D1 oncogene is a key regulator of cell cycle progression associated with various human malignancies. Aim: To establish the prognostic significance of cyclin D1 in oral squamous cell carcinoma (OSCC) and to correlate its association with clinicopathological parameters. Materials and Methods: A retrospective study was carried out on 50 previously histopathologically diagnosed, formalin-fixed, paraffin embedded (FFPE) tissue samples of OSCC. Immunohistochemical analysis was performed in 50 cases of different grades of OSCC using a commercially available monoclonal anti-cyclin D1 antibody. Statistical Analysis Used: All the compiled data was statistically analyzed using Chi-square and Mann-Whitney test. P values of <0.05 were considered to be significant. Results: Overexpression of cyclin D1 was seen in 68% cases of OSCC with a significant correlation with younger age group; no correlation was reported with respect to gender and site. The intergroup comparison of the cyclin D1 expression between well with poorly differentiated OSCC exhibited a significant correlation. Conclusions: The relative contribution of cyclin D1 expression in OSCC was significant according to the present study and further needs to be determined in large cohorts.