This study was aimed at defining the therapeutic value of percutaneous ethanol injection in patients with solitary hepatocellular carcinoma less than 4 cm. Ultrasound-guided ethanol injection was performed in 24 cirrhotic patients (9 Child A, 10 Child B and 5 Child C), with hepatocellular carcinoma not suitable for surgical treatment. Its efficacy was assessed by repeated ultrasound, computed tomography and tumor biopsy during a follow-up ranging between 4 and 41 mo. Ethanol injection did not achieve a complete tumor necrosis in five cases after a minimum of 12 injections. Seven of the remaining 19 cases, with initial success, have shown recurrence during follow-up, thus resulting in 50% success rate, which was significantly related to baseline tumor size. The six patients with nodules less than 2 cm achieved a complete response, whereas this was recorded in 2 of the 7 with tumor size between 2 and 3 cm, and in only 1 of the 11 cases between 3 and 4 cm. The 1- and 2-yr survival of Child's A and B patients was 87% and 70%, respectively. These results indicate that percutaneous ethanol injection is a useful treatment for hepatocellular carcinoma, especially in tumors less than 3 cm. The high survival rate among patients with nonadvanced liver disease suggests that this therapeutic approach can be considered an alternative approach to surgical resection for tumors smaller than 3 cm.