—Histoplasma capsulatum var. capsulatum is a neurotropic dimorphic fungus. The majority of immunocompetent infected individuals have either no symptoms or a very mild illness. CNS involvement is observed in 5% to 10% of patients, mostly in case of disseminated histoplasmosis and/or in association with immunecompromising conditions. Radiologic differential diagnosis of a ring-enhancing intraparenchymal brain mass lesion should include also histoplasmosis. Biopsy remains the gold standard for diagnosis, but non-invasive strategies, such as detection of fungal antigens in cerebrospinal fluid, may be helpful. Liposomal amphotericin B followed by itraconazole for at least 1 year is recommended, but often associated with significant side effects.