The prognosis for pediatric patients with hepatocellular carcinoma is poor, except for fewer than half the patients, who can be rendered disease-free with conventional liver resection. Multicentric, bilobar liver cancer remains unresectable, even after radiation and chemotherapy. Liver transplantation alone for primary hepatic cancer has had limited success. Chemotherapy has been reserved for use after transplantation, with little demonstrable benefit. A pilot program of pretransplant chemotherapy was undertaken. Four adolescent patients with unresectable, multicentric, bilobar hepatocellular carcinoma were staged noninvasively, underwent chemotherapy followed by a final staging laparotomy, and then had liver transplantation. Three of the four patients survived and have no evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44 months after transplantation. Pretransplant chemotherapy has four potential advantages: (1) minimized risk of posttransplant opportunistic infections, (2) less tumor bulk at the time of transplantation, (3) fewer local recurrences, and (4) a lower rate of metastasis.