Histoplasma capsulatum is endemic to the Ohio and Mississippi River valleys. Exposure to H. capsulatum is very common in this region and usually follows a benign clinical course. However, immunocompromised hosts, like those with HIV/AIDS, are more susceptible to symptomatic infection, and have a greater chance of developing disseminated disease. We report an unusual case of a patient with AIDS presenting with a single ring-enhancing brain lesion and a focal neurological deficit. Workup was unrevealing, and brain biopsy was felt to represent too much risk as the lesion was located at the right tegmentum. The lesion enlarged over a period of months, and he underwent radiation therapy after the lesion caused obstructive hydrocephalus. He expired soon after completion of radiation therapy. At autopsy, the mass lesion was noted to contain organisms constant with H. capsulatum, pathologically consistent with a histoplasmoma.