Dysregulation of the epidermal growth factor receptor (EGFR) is one of the most frequently studied molecular events leading to oral carcinogenesis. Overexpression of EGFR is a common event in many human solid tumors. Elevated levels of EGFR mRNA in human cancer occur with and without gene rearrangement. Structural alterations in the receptor can also result in the dysregulation of the EGFR pathway. EGFR overexpression without gene re-arrangement is frequently observed in human oral cancers. However, little is known whether structural alterations in the receptor or perturbations in the EGFR pathway contribute to oral carcinogenesis. Several preliminary studies suggest that EGFR-targeted therapeutic approaches might be successful in controlling oral cancer.