The bcl-2 proto-oncogene was first discovered in B-cell lymphomas and is the prototype of cell death regulatory genes. It's gene product, the bcl-2 protein, directly or indirectly inhibits the release of cytochrome C, thus preventing the activation of caspases and hence, inhibiting apoptosis. This leads to cellular immortalization, contributing to formation of the tumour and facilitating the permanent acquisition of mutations. Studies show increased expression of the bcl-2 protein in about 50% of human cancers. Keeping this in view, our study was undertaken to evaluate the expression, to quantify and to determine the intensity and the pattern of bcl-2 in various histological grades of Oral Squamous Cell Carcinoma. Method: The present study investigated the immunohistochemical expression of bcl-2 in 38 cases, of which 32 were histologically diagnosed as Oral Squamous Cell Carcinomas and 5 normal lymph nodes along with 1 normal oral mucosa were included as controls. Each specimen was sectioned at 3 micron thickness, immunostained with the bcl-2 antibody and viewed under a light microscope. Results: All the 38 cases showed bcl-2 immunopositivity. The number of bcl-2 positive cells was more in poorly differentiated SCC than in well differentiated SCC. The intensity of bcl-2 expression was more in moderately differentiated SCC, while in poorly differentiated SCC, an equal number of cases showed light and dark intensity. When the distribution pattern of bcl-2 expression was assessed, the tumour islands devoid of central keratinization showed bcl-2 expression in all the tumour cells. Summary and conclusion: In OSCCs, the number of cells expressing bcl-2 increased from well differentiated to poorly differentiated, showing an inverse relationship with the degree of differentiation. Further correlative studies using markers for other members of the bcl-2 family are necessary to elucidate the specific molecular defects critical to the biology of this tumour, which will have an impact on it's diagnosis and treatment.