Background: E-cadherin plays an important role in cell-to-cell adhesion and in maintaining the structural integrity and its loss is associated with increased invasiveness and metastatic ability. The aim of this study was to compare E-cadherin expression in oral squamous cell carcinoma and follicular ameloblastoma. Material and Methods: 19 Specimens of Oral squamous cell carcinoma (OSCC) of different grades& 15 specimens of follicular Ameloblastoma (AB) in the form of paraffin blocks were subjected to Immunohistochemistry to detect E-cadherin expression, E-cadherin immunoreactivity was correlated with grades of differentiation and with clinicopathological features. Results: E-cadherin immunoreactivity was found to inversely correlate with the loss of cell differentiation. There was no significant difference recorded between the AB versus grade 1 OSCC (p=0.3545), There was a very significant difference recorded between the AB versus grade 2 OSCC (p=0.009), There was an extremely significant difference recorded between the AB versus G3 OSCC (P<0.0001). Conclusion: Reduction or loss of E-cadherin has been found to be correlated with the degree of de-differentiation suggesting a potential prognostic factor for malignancies.