Background: E-cadherin plays an important role in cell-to-cell adhesion and cell motility and its loss is associated with oral squamous cell carcinoma (OSCC) progression. The aim of this study was to determine the expression of E-cadherin in various grades of OSCC and to correlate changes in the expression between these various grades. Material and Methods: Immunohistochemical staining with Streptavidin peroxidase was used to analyze the E-cadherin expression in 24 cases of oral squamous cell carcinoma. Nine cases of well differentiated OSCC, 6 cases of moderately differentiated carcinoma and 9 cases of poorly differentiated OSCC. Results: E-cadherin immunoreactivity was found to inversely correlate with the loss of cell differentiation. The highest degree of E-cadherin expression was detected in (100%) cases of well differentiated OSCC. Followed by (100%) cases of moderately differentiated and (66.7%) cases of poorly differentiated OSCC. Conclusion: Loss of the cell adhesion and E-cadherin plays an important role in progression of OSCC, that is, down regulation of its expression is associated with advanced grades of OSCC.