The majority of oral squamous cell carcinoma (OSCC) is preceded by oral premalignant lesions (OPL). The transition of premalignancy into invasive carcinoma necessitates the remodeling of the extracellular matrix (ECM) and basement membrane which may be the first step of local invasion. This remodeling is mediated by various soluble and cell surface molecules, including extracellular matrix metalloproteinase inducer (EMMPRIN).Since EMMPRIN plays such an important role in epithelial-connective tissue interactions, the expression patterns of EMMPRIN were estimated in normal oral mucosa, epithelial dysplasia and in different grades of OSCC in order to evaluate its role in cancer progression.In the current study, immunohistochemical staining using anti EMMPRIN antibody was conducted on 45 paraffin-embedded specimens of oral epithelial dysplasia (OED) and oral squamous carcinoma (OSCC) and compared with normal oral mucosa.The positive immunoreaction of EMMPRIN was detected in both epithelium and underlying connective tissue. It was located at the cell membrane or appeared as a granular cytoplasmic reaction.Generally, the expression of EMMPRIN was significantly greater in OSCC followed premalignant lesions than in the normal oral mucosa.As EMMPRIN is actively involved in tumor growth, invasion and metastasis, its measurement may be helpful in predicting patients' prognosis.