A chronic hepatitis B virus (HBV) carrier with diffuse nodular transformation of the liver and malignant lymphoma in the lymph nodes and spleen developed massive hepatic necrosis and died three weeks after the third cycle of chemotherapy. Immunosuppressive drug treatment may favor replication of HBV, resulting in massive hepatocyte destruction when the immune response recovers following withdrawal of chemotherapy. This outcome must be considered in patients with chronic hepatitis B who are treated with a course of prednisone followed by antiviral therapy as well as in HBV carriers following chemotherapy for malignant disease.