A 46-year-old man presented with a history of personality change and memory disturbance for 5 months. He gradually became difficult in doing a daily job. Brain MRI showed abnormal hyperintensity within bilateral mesial temporal lobes on T2 weighted image. Therefore, viral and autoimmune limbic encephalitis was initially suspected. However, because treponemal and non-treponemal specific antibodies were positive in serum and cerebrospinal fluid (CSF), the diagnosis of neurosyphilis was made. Patients of neurosyphilis with mesiotemporal T2 weighted hyperintensity reportedly showed common features such as relatively young age, HIV-negative, subacute cognitive impairment and seizure, as seen in our patient. Neurosyphilis should be included in the differential diagnosis for mesiotemporal abnormality in patients with these features. In addition, in our patient, anti-glutamate receptor ε2 antibody (ELISA) was strongly positive in CSF that suggested additional autoimmune pathophysiological mechanism.