Purpose:The extent of invasion can be analyzed by the expression and production of various genes and proteins by lesional cells. However, current clinical parameters lack the potential to predict the neoplastic behavior in solid ameloblastoma (SAB) and odontogenic keratocyst (OKC). Cortactin, an F-actin binding protein, overexpression has been correlated with advanced clinic pathological stage and poor prognosis in several tumors. E-cadherin belongs to the classical cadherins which. Low E-cadherin expression correlated to aggressive, poorly differentiated, high-grade carcinomas and low patient survival. Human-murine double minute 2 (MDM2), contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance, overexpression of MDM2 has been observed in various human cancers and can contribute to genomic instability, thus, further promoting tumorigenesis. The purpose of this work was to investigate the role of Cortactin, E-Cadherin, MDM2 proteins expression in SAB and OKC and correlate the expression of these markers with the aggressive behavior of these tumors. Material and method: 10 case of solid ameloblastoma with its different histologic variants and 10 cases of the keratocystic odontogenic tumor were collected as paraffin embedded blocks. An immunohistochemical investigation using, Cortactin, E-Cadherin, and MDM2 antibodieswere done for all specimens. Results: The mean area percent of immunoexpression of Cortactin was greatest in SAB while, the mean area percent of immunoexpression of E-Cadherin, MDM2 were greatest in OKC. Conculsion:According to the current study, the absence of any significant differences between AB and OKC indicate the neoplastic and aggressive nature of OKC similar to AB.