Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are denned as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related sMn and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure.