We reported a low prevalence (11%) of p53 expression detected by immunohistochemistry in oral squamous cell carcinomas associated with betel/tobacco chewing Sri Lankans (23). Five neoplasms which over-expressed p53 protein were used in the present study of mutations. Despite extensive sequence analysis no mutations were detected in exons 5 through 9 of the p53 gene in all the DNA samples of these neoplasms. Thus, over-expression of p53 is not necessarily synonymous with mutations in the exons studied, although mutations of this gene have been reported in oral and head and neck cancer from Japan and USA. The absence of mutations in betel/tobacco related carcinomas in this population may derive from differences in aetiology, carcinogen metabolism and susceptibility, DNA repair mechanisms and/or genetic predisposition.