This report describes a 63-year-old man with a large adenomatous hyperplasia that had been followed over 10 years without any apparent change of size or profile, but grew rapidly after completion of interferon therapy. This patient was a sustained responder, in whom serum alanine aminotransferase levels remained within the normal range and the serum hepatitis C virus-RNA level was undetectable after completion of interferon therapy. However, the tumors, located in segments 5 and 8 of the liver, which had both been followed as adenomatous hyperplasia, grew rapidly two months after completion of interferon therapy; imaging modalities revealed that the former was a typical hepatocellular carcinoma and the latter a large adenomatous hyperplasia. The patient underwent right paramedian sectoriectomy of the liver. Histological examination showed that the tumor in segment 8 had mosaic proliferation of hepatocytes without fibrosis, indicating adenomatous hyperplasia, in which a small focus of well-differentiated hepatocellular carcinoma was present. This case suggests that even in sustained responders to interferon, administration of this drug cannot suppress malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. One year after surgery, the patient is doing well without signs of recurrence.