Oral premalignant lesions OPL are lesions that can potentially transform into malignancy in a variety of tissues, including the oral cavity. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers. Podoplanin (D2-40), a newly reported monoclonal antibody that recognizes human podoplanin, was introduced as an excellent immunohistochemical marker of lymphatic endothelial cells in investigations of neoplasms of lymphatic origin within neoplastic tumors. The vascular endothelial growth factor A (VEGFA) is a strong positive regulator of angiogenesis that stimulates endothelial cell functions needed for new blood vessel formation, such as endothelial migration, differentiation and endothelial cell proliferation. The present study investigated the immunohistochemical expressions and correlations of podoplanin and VEGFA with studied cases. The expressions of podoplanin and VEGFA in 20 cases of OPL and 20 cases of OSCC studied cases were determined immunohistochemically. The findings of the present study revealed high statistically significant correlation between degree of dysplasia as well as clinical forms of OPL studied cases, tumor differentiation and lymph node involvement of OSCC studied cases with podoplanin expressions. VEGFA expression revealed high significant correlation with clinical forms of OPL studied cases, tumor differentiation and lymph node involvement of OSCC studied cases. These results suggest that podoplanin and VEGFA may be predictor of early oral tumorigenesis and for malignant transformation risk assessment of OPL and as biomarkers for advanced grades of OSCC may be useful to identify OSCC patients at risk of a more unfavorable clinical outcome.