Ki67 immunoreactivity, p53 expression and apoptotic index were examined in 26 non-malignant lesions of the head and neck region, 22 dysplastic lesions of patients without evidence of head and neck carcinoma during follow-up time, 24 dysplastic lesions of patients who subsequently developed a squamous carcinoma in the same area, and 42 squamous cancer cases. A directly proportional relation between Ki67 immunoreactive pattern, apoptotic index and histological evolution from normal to dysplastic or neoplastic mucosa was evident. As far as p53 protein is concerned, its expression became higher and frequently transmural in neoplastic mucosa. A strict correlation between frequency and density of Ki67/p53 immunoreactivity according to invasive cell grading (ICG) scores and poor prognosis of patients were found. On the contrary, malignant cells highly expressing p53 seemed not to undergo apoptosis. Ki67 antigen and p53 protein detection in premalignant lesions and in carcinomas of the head and neck tract could be a useful marker for the management of patients at risk.