A 27-year-old woman, who had emigrated from Sierra Leone 5 years prior, presented with worsening headaches of 3-month duration. Magnetic resonance imaging of the brain revealed a lobulated mass lesion with central necrosis in the right parietal and occipital lobes. Biopsy was performed, and histopathology revealed multiple granulomas. Although acid-fast stain of the tissue was negative, gene probe showed Mycobacterium tuberculosis complex, and culture revealed Mycobacterium africanum. This species is rare in the United States, and to the best of our knowledge, this is the first reported case of M. africanum causing a brain mass.