Mutations of the p53 gene are the most common genetic abnormality described in human cancer; p53 mutations have recently been reported in more than half of the cases of squamous cell carcinomas of the skin. We have previously reported positive p53 immunostaining in Bowen's disease and actinic keratosis. To determine if this abnormal immunostaining reflects p53 mutation or alternative pathways of p53 protein inactivation we Wave performed direct sequencing of p53 in 20 further cases of Bowen's disease. We found eight mutations in 20 cases, seven of which would produce alterations in the p53 protein product. Our results suggest that p53 mutation is an early event in malignant conversion, frequently preceding invasion in squamous cell neoplasia of the skin. The type and site of the observed mutations reflect known mutational hotspots and support the role of ultraviolet radiation in the pathogenesis of these tumors.