The objective of this review is to determine whether the p53 tumor suppressor gene plays a role in the development of head and neck cancer. Mutations in the p53 tumor suppressor gene have been shown to be one of the most common genetic abnormalities in human cancers, and the published literature also shows this to be the case in head and neck cancer. Initial investigations into p53 gene expression in head and neck cancers indicated that about 60% overexpressed this gene, which was substantiated by many of the later reports. On analysis of all of the published data, mutations in the p53 gene have been found in exons 4 through 9, with a hot spot in the 238-248 region. Overexpression of p53 gene has not been found to correlate with any of the clinicopathologic parameters or survival (calculated from the date of diagnosis), but it does correlate with a history of heavy smoking and drinking. The p53 gene appears to have a role in both the early and late stages of this disease. Overexpression of p53 was found in the tumors of patients who had stopped smoking 5 to 18 years before their cancer developed; also, the overexpression of p53 has been shown in dysplastic and carcinoma in situ lesions of the larynx. Furthermore, overexpression of this gene was found to correlate with a very poor outcome in a group of patients classified with "end-stage disease." A model is proposed to describe the role of p53 in the development of squamous cell carcinoma of the head and neck.