MDM2 (murine double minute gene 2) overexpression has been implicated in the pathogenesis of human tumors via inhibition of the p53 tumor suppressor protein. To investigate the potential involvement of MDM2 overexpression in the pathogenesis of oral squamous cell carcinomas (SCCs) in Taiwan, we examined the expression of MDM2 protein and its relationship to p53 protein levels in 52 oral SCCs using antibodies to MDM2 and p53. Of the 52 patients, 36 (69 %) had tumors with positive MDM2 nuclear staining and 32 (61%) had tumors with p53 nuclear staining. Co-expression of MDM2 protein and p53 was detected in 25 (48%) cases; and 9 (17%) tumors showed neither MDM2 protein nor p53 staining. A significant correlation was observed between MDM2 protein and p53 expression in 38 cases with an areca quid (AQ) chewing habit (P=0.032). No significant correlation was found between the degree of MDM2 protein staining and the patients' ages, sex, cancer location, clinical staging, primary tumor TNM status or histological differentiation of SCC at the time of initial presentation. Kaplan-Meier analysis showed that either MDM2 protein expression or co-expression of p53 and MDM2 protein did not relate significantly to patient overall survival. Nevertheless, the high prevalence of MDM2 protein overexpression found in this study suggest that MDM2 may also participate in the carcinogenesis of AQ chewing-associated oral SCCs in Taiwan.