This review summarises serologic profiles and clinical features of HCV infection in children with leukemia. The diagnosis of HCV infection is currently based on the detection in serum of antiviral antibodies and HCV-RNA. Studies on leukemic children, however, have clearly shown that only HCV-RNA testing correctly identifies HCV infection, as specific antibodies become detectable in serum only after chemotherapy withdrawal in almost all cases. Viraemia instead appears early in the course of leukemia, and infected patients become carriers. The pattern of liver disease is rather homogeneous. Early onset, persisting ALT elevation during chemotherapy often with drastic reduction during high-dose chemotherapy, followed by sharp exacerbations of liver cell necrosis. ALT normalise after chemotherapy withdrawal in most cases, despite persisting viraemia. As regards to the ultimate prognosis of liver disease in these children, we have observed that, among a series of 119 patients followed for at least 10 years off-therapy, none has developed clinical decompensated liver disease and only 6% still has abnormal ALT levels. On the other hand, the need for prolonged follow-up of children surviving leukemia with chronic HCV infection is emphasized by the fact that the natural history of HCV infection has not been fully clarified and that additional late sequelae are likely to occur.