Ameloblastoma is characterized by heterogeneity regarding its pathogenetic development, molecular abnormalities, and clinical course. Determining the molecular basis underlying these important differences remains challenging. Nevertheless, identifying molecules that influence tumor behavior would be the first steps towards gaining some insights into its pathobiology. MDM2, a 90-95kDa protein coded by a mdm2 gene which is mapped on chromosome 12q13-14. MDM2 is a negative regulator of p53 activity, through binding to the transcriptional activation domain of p53 leading to proteasome-mediated degradation, Cortactin, a product of CTTN gene, mapped to human chromosome 11q13 regulates actin-related (Arp2/3) complex induction of actin polymerization during invadopodia formation, thereby promoting cell motility. This has been accomplished through its involvement in all steps of the invadosome lifecycle, from the assembly, maturation, proteolytic activity, and disassembly. This study aims to evaluate the association of both MDM2 and Cortactin expression in solid ameloblastoma and its malignant counterpart and analyzing their significance. 10 cases of SAB with its different histologic variants and 20 cases malignant variants of ameloblastoma tumors were collected. An immunohistochemical investigation using, Cortactin, and MDM2 antibodies were done for all specimens. There was a statistically significant difference between malignant group and benign group. According to the current study Cortactin and MDM2 can be useful when considering the diagnosis of malignancy.