Aims: To assess p53 protein expression in a range of odontogenic cysts arising in the mouth, including those of developmental and inflammatory origin. Methods: p53 protein was identified using the polyclonal antibody CM-1, together with a standard immunoperoxidase technique. A total of 36 cystic lesions were examined, all of which were histologically benign. Results: Expression of p53 protein was identified within the lining of five of 12 odontogenic keratocysts but was not detected in the other cystic lesions in the series. Conclusions: This is believed to be the first report that identifies increased expression of p53 protein in benign cystic epithelium. The increased expression of p53 protein in the nucleus is usually associated with malignant disease. These findings are relevant to the management of odontogenic keratocysts which have a tendency to recur, and also to Gorlin Goltz syndrome in which keratocysts and multiple basal cell carcinomas are features.