Squamous cell carcinoma(SCC) of Syrian golden hamster buccal pouch is the best animal model that is histogenetically and morphologically similar to events involved in the development of SCC in human oral cavity. Mutation of the p53 gene is a common event in many human cancers and is also found in certain rodent tumors. Thirty-five SCCs of the buccal pouch of Syrian hamster induced by topical treatment of 7, 12-dimethylbenzanthrancene(DMBA) for 16 weeks were sectioned and examined for potential alterations of p53 expression and PCNA by immunohistochemical methods. Twenty normal control hamsters without DMBA treatment and 25 each hamsters with DMBA treatment for 4 and 8 weeks were also examined. In the mucosa of normal control animals, there was no p53 expression. In hyperplastic mucosal lesions(4 weeks DMBA exposure), the p53 positivity was limited to the basal cell layer and in dysplastic lesions(8 weeks DMBA exposure), the p53 positivity was expanded to the parabasal and superficial layers. In SCCs, p53 staining was diffusely positive in all 35 hamsters. The staining patterns and distribution for p53 protein immunostaining were similar to those of the PCNA staining. These results suggest that p53 and PCNA alterations occur in a multistep fashion during syrian hamster oral cavity carcinogenesis. Since mutation of the p53 gene and increased PCNA activity appear to be an important step in the pathogenesis of DMBA-induced hamster cheek pouch SCC, one may surmise that similar pathogenetic changes may occur in human oral cavity SCC. Therefore, p53 alteration and PCNA positivity can be utilized for risk assessment and may serve as biomarkers or oral carcinogenesis in both Syrian hamsters and humans.