In this study we have investigated the prevalence of p53 overexpression in various vulvar lesions and its significance as a prognostic parameter in patients with vulvar carcinoma. Overexpression of p53 was studied in 66 patients with squamous cell carcinoma of the vulva and in the following synchronous epithelial lesions: intraepithelial neoplasia grade I (VIN I) (n = 33), VIN II (n = 11), VIN III (n = 16), lichen sclerosus (n = 30), squamous cell hyperplasia (n = 37), normal vulvar skin of patients with vulvar carcinoma (n = 55), and in 18 samples of normal skin from healthy controls. Survival curves of the p53-positive and p53-negative patients were compared using the log-rank test. The use of DO7, and anti-p53 monoclonal antibody, showed p53 overexpression in 35 (53%) specimens of carcinoma, in eight (27%) of lichen sclerosus, in five (14%) of squamous cell hyperplasia, in six (18%) of VIN I, in two (18%) of VIN II, in two (13%) of VIN III, and in seven (13%) specimens of normal vulvar skin. Staining of normal skin from healthy controls showed no p53 positive specimens. No relationship between expression of p53 and disease-free survival in patients with vulvar carcinoma was present. In malignant, synchronous premalignant and non-neoplastic epithelial disorders of the vulva, p53 overexpression is a frequent observation, indicating that the latter two groups have characteristics of premalignant lesions. In addition, p53 overexpression was not a useful prognostic parameter for patients with vulvar carcinoma.