To understand the timing of p53 overexpression in oral carcinogenesis, we performed immunohistochemistry for p53 on 118 biopsy specimens containing various oral precancerous and cancerous lesions. The immunoreactivity for p53 protein was found in the nuclei of the parabasal layer in hyperplastic and precancerous lesions which increased according to the degree of dysplastic change. The overexpression of p53 protein reached the maximal frequency of 76% in squamous cell carcinoma. Moreover, proliferative activity was also evaluated by means of Ki-67 immunohistochemistry and the histochemical count of argyrophilic nucleolar organizer regions (AgNORs). Although these proliferation markers tended to increase in number according to the severity of oral lesions, they were weakly correlated with the results of p53 immunohistochemistry. Our results indicate that p53 overexpression is an early event in oral carcinogenesis never influencing the proliferative advantage in oral precancerous lesions.