The present study addressed the impact of human papillomavirus (HPV), p14, and the product of the retinoblastoma gene (pRb) in vulvar carcinoma in relation to other clinicopathologic variables and prognosis. We immunohistochemically studied 217 primary tumors from patients with vulvar carcinoma for the expression of pRb and p14. By the use of in situ hybridization, the primary tumors and 7 lymph node metastases were studied for the presence of HPV-16, HPV-18, HPV-31, and HPV-33 DNA. HPV-infected cases significantly correlated with high expression of p14 (P < .01) and p16 (P < .01). In HPV- cases with high expression of p53, no p14 expression predicted the poorest disease-specific survival (P < .01). For the first time, we have shown that p14 expression indicates longer disease-specific survival in patients with vulvar carcinoma. In patients with HPV- tumors expressing high levels of p53, low p14 indicated the poorest 5-year disease-specific survival.