The treatment of patients with cirrhosis and hepatocellular carcinoma (HCC) has improved dramatically over the past 10 years. We conducted a 6-year prospective study, using multimodality ablation therapy (MMT) combined with liver transplantation (LTx) for patients with cirrhosis and unresectable HCC. Subjects were classified as: group 1 (n = 35), intention to treat with MMT + LTx; group 2 (n = 16), contemporaneous LTx with "incidental" HCC on explants; group 3 (n = 94), MMT alone; and group 4 (n = 19), palliative care alone. MMT included trans-arterial chemo-embolization (54.4%), trans-arterial chemo-infusion (28.6%), and radio frequency ablation (17%). Group 1, with a mean wait time of 11.6 months pre-MELD era and 5.4 months post-MELD era, had a mean of 2.4 +/- 1.2 MMTs and achieved 1- 3-, and 5-year patient survivals of 100, 100, and 76%, respectively, which was not different from group 2 (incidental HCC), namely 93, 93, and 93%, respectively; or to a contemporaneous non-HCC LTx group: namely 84.3, 78.7, and 73.9%, respectively. Despite careful pretransplant HCC staging, 22.8% (8 of 35) group 1 subjects were understaged. Those subjects in group 1 with true T1-2 stage HCC achieved 100% cancer-free survival at 5 years. Only three cases of HCC recurrence occurred in our series, all of whom were understaged. Our data suggest that pretransplant MMT followed by timely LTx provides excellent disease-free survival at 5 years for patients with true T1-2 stage HCC and cirrhosis. Pretransplant HCC understaging contributes to posttransplant HCC recurrence after LTx.