Chronic active Epstein-Barr virus (EBV) infection, which is considered to be a childhood disease, often develops into natural killer (NK) or T-cell lymphoma after recurrent infectious mononucleosis (IM)-like symptoms. We describe a 56-year-old woman who developed NK-cell lymphoma after 9 months of recurrent IM-like symptoms. The patient had an unusual anti-EBV antibody profile. Increased levels of EBV genome were detected in the liver and peripheral blood. Several chemotherapy regimens were ineffective, and the patient died of progression of lymphoma. Certain subtypes of NK-cell lymphoma showing a long-lasting prodrome related to chronic EBV infection may exist.