The tumour‐suppressor protein p53 is mutated in many head and neck squamous cell carcinomas (HNSCCs). In this immunohistochemical study, similar numbers of p53‐overexpressing cells were uniformly distributed throughout normal oral epithelium, irrespective of different smoking habits or the presence of an adjacent HNSCC. In a previous study, an increased number of proliferating cells were observed in normal oral mucosa from (ex)‐smoking individuals and the present observations indicate that overexpression of p53 does not play a role in this increase. In contrast, focally overexpressed p53 occurred more frequently (p < 0·05) in the tumour‐adjacent normal mucosa (TAM) from smoking HNSCC patients (50 per cent) than in that from non‐smoking HNSCC patients (20 per cent). This increase in focal p53 overexpression might represent an early alteration in the development of HNSCC, but it could not be detected in mucosa from healthy smokers. This indicates that besides the abuse of tobacco, other environmental and/or genetic factors must contribute to the presence of p53‐positive clusters in TAM. Abuse of alcohol, an additional factor in these HNSCC patients, together with the abuse of tobacco, might play a role in the development of the p53‐positive clusters. Copyright © 1999 John Wiley & Sons, Ltd.