Hypertrophic genital herpes is a disfiguring manifestation of a common infection seen in immunocompromised hosts that can be clinically mistaken for malignancy. We review the literature and describe hypertrophic genital herpes in a human immunodeficiency virus-positive patient receiving antiretroviral therapy. Treatment with valacyclovir, cidofovir, and foscarnet failed, but thalidomide treatment was successful.