Autoimmune hematologic abnormalities are not well recognized in chronic hepatitis C virus infection. We demonstrate an unusual association between primary autoimmune hemolytic anemia and chronic hepatitis C virus infection. A 69-year-old woman who had a history of hepatitis C virus-related liver cirrhosis was found to have deteriorating anemia with reticulocytosis when admitted to the hospital. Laboratory work revealed both positive direct and indirect Coombs' tests, and warm-type immunoglobulin G against surface antigens of red blood cells. After prednisolone therapy, her anemia improved dramatically. To our knowledge, this is the first reported case of chronic hepatitis C virus infection linked with autoimmune hemolytic anemia in its natural course, not related to prior interferon treatment. Our report suggests that isolated autoimmune hemolytic anemia may be one of the unusual hematologic manifestations of chronic hepatitis C virus infection.