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Background: Podoplanin is a mucin-like transmembrane glycoprotein that been highly and specifically expressed in the lymphatic endothelial cells, but not in the endothelium of blood vessels. Studies have shown that podoplanin expression in tumor cells including those of squamous cell carcinomas and a relationship with the clinicopathological features. This raises a possibility that podoplanin might have a biological function in oral squamous cell carcinoma and its expression could be used as a biomarker for diagnosis and prognosis. Methods: Formalin-fixed paraffin-embedded tissue blocks and histopathology reports of 50 cases of OSCC were used in this study. These were evaluated immunohistochemically for the expression of podoplanin using D2-40, a monoclonal antibody. The association between podoplanin expression and tumor site, size and degree of differentiation, lymph node metastasis, and prognosis was analyzed. Results: In this study, we observed that podoplanin was highly expressed in OSCC, but we found no significant association between podoplanin expression and clinicopathological characteristics and survival. Conclusion: The role of podoplanin as a marker for lymph node metastasis is questionable. To determine the role of podoplanin as a prognostic marker, further prospective studies are required with a longer follow-up period. Further studies using a combination of markers are required to predict tumor invasiveness and occult metastasis in OSCC.