Clinical features of hepatocellular carcinoma (HCC) with normal serum alpha-fetoprotein (AFP) levels were compared with those of AFP-positive cases. A total of 606 patients were divided into four groups based on their serum AFP levels at the time of diagnosis: group 1 (less than or equal to 20 ng/ml, N = 125), group 2 (20-1000 g/ml, N = 256), group 3 (1000-10000 ng/ml, N = 149), and group 4 (greater than 10000 ng/ml, N = 76). Increasing prevalence of group 1 patients and decreasing prevalence of group 4 were noted during the last 9 years. The proportion of hepatitis B virus-positive cases was significantly lower in group 1 than in group 4. The serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase ratio was found to be significantly higher in group 4 than in group 1 regardless of the size of the tumors. The survival rates were compared among the four groups in size matched cases since the size of the tumor significantly influenced their prognosis. The median survival in relatively small HCC patients (less than or equal to 5 cm in diameter, N = 199) were 24.6 months for group 1, 20.6 months for group 2, and 13.7 months for group 3 patients; and those in large HCC (greater than 50% in the proportion of the tumor area, N = 200) were 15.1 months for group 1, 6.3 months for group 2, 5.8 months for group 3, and 5.2 months for group 4. Thus, serum AFP values at the time of presentation are not only of diagnostic value, but also of prognostic significance in patients with HCC.