The brain gumma is a rare manifestation of the tertiary stage of syphilis. A case of neurosyphilitic gumma was confirmed by the Treponema pallidum polymerase chain reaction in a 46-year-old HIV-positive homosexual man. The patient presented with a severe headache and was hospitalized. A computed tomography scan was performed which revealed a left frontal lobe mass. Lymphoma was suspected. However, infectious disease diagnostics were performed on the cerebrospinal fluid that included investigations for syphilis and other microbiological agents such as Toxoplasma gondii. This revealed a reactive venereal disease research laboratory test, a reactive syphilis rapid plasma reagin and a reactive T. pallidum particle agglutination test. The patient was treated for syphilis till complete recovery.