This report presents two HIV-infected women who developed invasive squamous cell carcinoma of the vulva. One patient was diagnosed with Stage II vulvar cancer 4 years after surgical excision of VIN. This patient underwent a hemivulvectomy and external-beam radiation therapy, but has subsequently developed recurrent vulvar cancer. The other patient was diagnosed with stage IV invasive vulvar cancer 1 year after the diagnosis of VIN and died of invasive vulvar cancer 11 months later. VIN should be considered a serious condition in HIV-infected women and clinicians should be careful to examine the vulva and perianal region in all HIV-infected women.