Isolated Kaposi sarcoma (KS) of the parotid gland is an uncommon but distinct entity in patients with human immunodeficiency virus type 1 (HIV-1). A 30-year-old white homosexual man in whom HIV-1 had been diagnosed 2 years previously developed right parotid gland enlargement in the absence of constitutional symptoms. He had been taking zidovudine, lamivudine, and indinavir; his CD4 cell count was 0.297 x 10(9)/L, and HIV-1 RNA load was 47 copies/mL. After surgical excision of the parotid gland, biopsy findings disclosed KS of an intraparotid lymph node. A literature review revealed 6 other men with HIV-1 and isolated parotid KS. To our knowledge, our patient is the first to have received triple antiretroviral therapy with excellent immunological and virological response and parotid gland enlargement that might reflect immune reconstitution. Even in the absence of skin or other lesions, KS should be considered in the differential diagnosis of parotid gland enlargement in patients with HIV-1, even in those who are responding to highly active antiretroviral treatment.