Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Although immunocompetent persons with H. capsulatum infections are usually asymptomatic, several clinical syndromes can manifest in immunocompromised patients. We report a case of a 61-year-old man with advanced HIV infection who presented with weight loss, anorexia, and renal failure. His symptoms were initially attributed to end-stage AIDS, but a more specific diagnosis was pursued. Bone marrow biopsy resulted in the discovery of disseminated histoplasmosis. This case illustrates the importance of actively pursuing the diagnosis of an opportunistic infection in persons with end-stage AIDS, treating the opportunistic infection aggressively, and maximizing the effectiveness of antiretroviral therapy.