This study was undertaken to examine the expression of p16 and p53 in vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma (SCC) of the vulva. We also analyzed the relationship between p16 and p53 immunoexpression in women younger vs. older than 55 years of age. Seventyseven histologic samples of vulvar tissue, treated surgically between June 2000 and November 2004 at the Complexo Hospitalar Santa Casa (Porto Alegre, Brazil), were investigated. We analyzed 28 cases of VIN, 37 cases of SCC and 12 normal vulvar tissues. The percentage of immunohistochemical positivity for p16 had the following distribution across the groups: VIN: 21.4% (6/28), cancer: 24.3% (9/37) and control: absent (p=0.202). p53 expression showed the following percentages: VIN: 60.7% (17/28), cancer: 18.9% (7/37) and control: 8.3% (1/12) (p=0.01). p16 expression in the cancer group (mean age: 63.4 years) was positive in 6 and 3 cases of women younger or older than 55 years, respectively (54.5% vs. 11.5%, p=0.01). p53 expression was not detected in young females with cancer, while it was expressed in 7/26 (26.9%) cases of the group of females older than 55 years of age (p=0.08). Our results suggest an increase in the immunohistochemical expression of p16 protein in young women with squamous cell carcinoma of the vulva, and a possible association with a low expression of p53.