Listeriosis is a foodborne disease that occurs mainly in the setting of cell-mediated immunosuppression. Histoplasmosis is a systemic fungal disease. It is usually self-limiting in immunocompetent individuals but occurs in the disseminated form in patients with acquired immunodeficiency syndrome. Concomitant invasive listeriosis and disseminated histoplasmosis have not been described previously. This case illustrates the complexities of diagnosing multiple infectious diseases in persons with acquired immunodeficiency syndrome and the vigilance to obtain a definitive diagnosis so as not to delay appropriate treatment.