The long-term evolution of hepatitis C virus (HCV) infection in oncologic and/or transplanted patients is still unknown. Patients treated for cancer are different from the general HCV-infected population because of the immunosuppression and the hepatotoxic treatments, which act as co-factors of liver damage. Recently it was observed that antimetabolites play a role in accelerating the process of hepatic fibrosis. The aims of this retrospective study were to describe the clinical course of chronic hepatitis C acquired during anticancer treatment in a group of patients referred to a single center, and to correlate the course of hepatic disease to the type of treatment they received. Among the 17 children who underwent very long follow-up (range 10-18.5 years), the authors identified a group with more active hepatic cytolysis through the serial observation of mean ALT values, HCV RNA determination, and histologic data when available. During follow-up, none of them developed hepatic failure, cirrhosis, or hepatocarcinoma. No single risk factor, such as exposure to antimetabolites, alkylating agents, or other chemotherapy, radiotherapy to the abdomen, exposure to other hepatotoxic drugs, appearance of vaso-occlusive disease, acute and/or chronic graft-versus-host disease, or length of immunosuppression, correlated with a worse course of hepatitis. No definitive conclusions can be drawn. However, multivariate analysis of hepatic risk factors in larger cohorts of patients will be able to provide us with more precise information about the clinical outcome of chronic hepatitis in survivors.