Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC <or= 5 cm or less than or equal to three HCCs <or= 3 cm. We prospectively evaluated the possibility of slightly extending these criteria in a down-staging protocol, which included patients initially outside conventional criteria: single HCC 5-6 cm or two HCCs <or= 5 cm or less than six HCCs <or= 4 cm and sum diameter <or= 12 cm, but within Milan criteria in the active tumors after the down-staging procedures. The outcome of patients down-staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention-to-treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down-staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow-up of 2.5 years after transplantation, the 1 and 3 years' disease-free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down-staging. The actuarial intention-to-treat survival was 27/48 patients (56.3%) in the down-staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down-staging criteria provide a comparable outcome to the conventional criteria.