A 65-year-old man presented with complaints of general malaise and severe disturbance of consciousness since 2 months prior to admission. MRI of the head showed high intensity area in FLAIR image in the left basel ganglia, the medial side of the left temporal lobe and both sides of the frontal lobe and brainstem. The contrasting effect was insignificant. Laboratory investigations showed positive results of EBV antibody titer and elevated EBV-DNA in the spinal fluid. We suspected encephalitis due to Epstein-Barr virus and the patient was treated with acyclovir and high dosage of steroids. However, the patient's consciousness gradually deteriorated and he died on day 146 of admission. Autopsy revealed proliferation of large atypical cells with clear and irregular nuclei in the brain tissue. Immunohistochemistry expressed positive EBER-ISH. This case was finally diagnosed as the central nervous system involvement by age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorder.