A 58-year-old woman from Zimbabwe, with a history of untreated human immunodeficiency virus, presented with leonine facies and a diffuse rash. The rash occurred in the context of a 1-year history of constitutional symptoms and cognitive decline. Laboratory investigations confirmed that her human immunodeficiency virus had progressed to acquired immunodeficiency syndrome. Through imaging, tissue biopsies, and polymerase chain reaction, a diagnosis of disseminated histoplasmosis was made. Since there was no history of travel and histoplasmosis is not locally endemic, the patient likely contracted this fungal infection more than 7 years ago, while living in Africa. We speculate that the histoplasmosis remained latent until her immune system began to decline. The work-up and management of this rare cutaneous presentation of a systemic disease, which should be added to the list of "great mimickers" in dermatology, are discussed.