This review describes three cases of human immunodeficiency virus-infected women who were diagnosed with vulvar cancer before age 40 years. A retrospective chart review was performed for three patients who were younger than 40 years of age and who had histologically confirmed invasive squamous cell carcinoma of the vulva diagnosed between 1999 and 2002. Demographic, clinical, and laboratory data were recorded. Three human immunodeficiency virus-seropositive women were diagnosed with invasive squamous cell carcinoma of the vulva, stages IA, IB1, and III. All cases were characterized by extensive surrounding vulvar, vaginal, and cervical intraepithelial neoplasia. CD4 cell counts were 250, 330, and 900 cells/uL. Two patients experienced previous acquired immune deficiency syndrome-defining illnesses: toxoplasmosis and cervical cancer. Vulvar cancer in young human immunodeficiency virus-seropositive women may be associated with other human papillomavirus-related diseases and immunosuppression, as evidenced by low CD4 counts and the presence of antecedent acquired immune deficiency syndrome-defining illnesses.