Systemic chemotherapy is generally ineffective in patients with advanced hepatocellular carcinoma (HCC). This could be partly explained by the frequent underlying cirrhosis, which induces serious toxicity requiring dose attenuation or drug discontinuation. We present observations of three patients with HCC developed in healthy liver and treated with docetaxel (100 mg/m(2) every 3 weeks in one patient; 30 mg/m(2) weekly, three times every 4 weeks in two patients). An objective partial response with long-term survival was obtained in all cases without severe toxicity. These results suggest that chemotherapy, and especially docetaxel, could be safe and effective in patients with HCC developed in healthy liver, and should be assessed in specific trials.