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A previously healthy 35-year-old man suffering from behavioral and mental deterioration for three months was referred to our facility. On admission, the patient was dysphasic and had tonic-clonic seizures. Neurological examination showed mental confusion, euphoric mood, mania, paranoia, and mild motor dysphasia. Magnetic resonance imaging (MRI) was performed twice but no abnormalities were revealed. His acute confusional state, elevated cerebrospinal fluid (CSF) protein, epileptic seizure and electroencephalogram showing intermittent frontal slowness were all suggestive of encephalitis. The patient was treated with acyclovir without significant improvement in his condition. Testing for herpes simplex virus and human immunodeficiency virus was negative. Limbic encephalitis was suspected and the patient was treated with intravenous immunoglobulin (IVIG) for five days. Venereal disease research laboratory and Treponema pallidum hemagglutination assay were both tested positive in serum and CSF. Neurosyphilis was diagnosed, and the patient received a 14-day course of penicillin G with gradual improvement. Anti-N-methyl-D-aspartate-receptor (anti-NMDAR) antibodies were positive in serum, confirming the presence of encephalitis. The atypical clinical presentation of neurosyphilis with symptomatology mimicking encephalitis and no MRI abnormalities made the diagnosis challenging. Coexistence of neurosyphilis with anti-NMDAR encephalitis has been reported only in one recent study. Our case demonstrates the importance of testing for syphilis in patients with unexplained neurologic deficits and suspected encephalitis.