Background: The expression of podoplanin is upâÂÂregulated in a number of different human cancers, including squamous cell carcinoma of the oral cavity and its relationship with tumor invasion raises the possibility that podoplanin expression could be used as a biomarker for diagnosis and prognosis. Aim: The aim of the present study is to evaluate the expression of podoplanin in different grades of squamous cell carcinoma (SCC) and to correlate the expression of podoplanin with relevant clinical features such as age, sex, site and associated habits. Materials and Methods: Retrospective study was carried on formalin fixed, paraffin embedded blocks of oral SCC (OSCC) from the archives of Department of Oral and Maxillofacial Pathology, Vishnu Dental College, Bhimavaram. Thirty diagnosed cases were included, of which 10 were wellâÂÂdifferentiated SCC (WDSCC) (n = 10), 10 moderately DSCC and 10 poorly DSCC. Demographics including age, sex, gender and associated habit history, were recorded. Immunohistochemical staining was done with podoplanin anti D2–40 antibody, for all the cases of OSCC and assessed qualitatively. The data obtained were tabulated and subjected to statistical analysis. Results: In the present study, 27 cases of SCC showed podoplanin expression and remaining three cases showed no expression. The scoring criterion suggested by Yuan et al. was followed for semiâÂÂquantitative assessment. OSCC, seven cases presented weak expression (Immunoreactive score [IRS] 0–3), 15 presented moderate expression (IRS Score 4–7) and 5 presented high expression (IRS Score > 8). The assessment of podoplanin expression in the cytoplasm, the membrane and the cytoplasm and membrane (both) of tumor cells showed overall high positivity in the cytoplasmic followed by both and the membrane. Conclusion: Podoplanin could be a potent biomarker in assessing the cytoplasm/membrane staining of tumor cells. Furthermore, a high level of podoplanin expression is suggestive of high frequency of lymph node metastasis and immature status in the differentiation process of OSCC.