Neurosyphilis presenting as a cerebral gumma is an uncommon event. To date there are seven cases of cerebral gumma reported in human immunodeficiency virus (HIV)-infected patients. We describe a HIV-infected patient with neurosyphilis presenting as an expanding central nervous system lesion and unremarkable cerebrospinal fluid analysis. This case report illustrates the clinical and therapeutic aspects of syphilitic gumma in HIV-infected patients.