Recent reports of p53 positivity in the normal mucosa of some head and neck cancer patients have been taken as evidence for field cancerization and hence a likelihood of the development of further tumours, yet few papers report the clinical significance of this finding through long-term follow-up. The immunohistochemical detection of p53 expression in clinically and histopathologically normal oral mucosa taken from the wound margin following excision of oral cancer was assessed using the polyclonal antibody CM1. Fresh frozen biopsies of normal oral mucosa and the corresponding tumour from 21 oral cancer patients and of normal mucosa from 25 non-cancer patients were assessed for p53 overexpression. The 'normal' mucosa was positive in 12 of the oral cancer patients and one of the non-cancer patients. Second malignant tumours were seen in patients from whom p53-positive 'normals' and p53-negative 'normals' were recorded. In five of the p53-positive 'normals', the corresponding cancer was p53-negative. In one case, where 'normal' mucosa was available from more than one site, one region was positive, whilst the other was negative. No obvious difference in age, tobacco use, or recurrence rate was seen between positive and negative cases. All patients who were still alive were reviewed for a minimum of 5 years. Using Fisher's exact test, no statistically significant difference was found for the rate of second malignant tumours occurring in patients with p53-positive compared with p53-negative normal mucosa. Thus, the detection of p53 in normal mucosa did not necessarily predict a further tumour.