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An isolated cranial nerve VI palsy is a rare initial manifestation of undiagnosed neurosyphilis. A 33-year-old male presented with a one month history of progressive headache and diplopia. Neurologic examination only revealed an isolated abducens palsy on the left. Cranial imaging was unremarkable. Examination of his cerebrospinal fluid revealed lymphocytic predominant leukocytosis and elevated protein. Microbiologic work-up were all negative. Further work-up revealed the patient to be serum Rapid Plasma Reagin and Enzyme Immunoassay reactive. Enzyme-linked immunosorbent assay for Human Immunodeficiency Virus also tested positive. His cerebrospinal fluid was then sent for Rapid Plasma Reagin to confirm the diagnosis of neurosyphilis. He completed 14 days of intravenous penicillin and was eventually discharged with partial resolution of the abducens palsy. We describe the second case of neurosyphilis presenting only with an isolated cranial nerve VI involvement. On further review, ours was the first case documented on an individual who had an undiagnosed Human Immunodeficiency Virus infection. There are various differentials for an isolated cranial neuritis but infectious causes, particularly neurosyphilis, should be considered among young individuals with known risk factors despite their apparently benign medical history.