It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eightynine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of &NO& of HCC (mean i SD, 3.26 2 1.23) was significantly higher than those of normal liver (1.37 f 0.13) and cirrhotic liver (1.49 5 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (>3.04) of Ag-NORs was significantly worse than that of those with a low number (53.04) of AgNORS. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement. (HEPATOLOGY 1995;21:393-397.) Nucleolar organizer regions (NORs) are loops of DNA that appear in the nucleoli of cells and that contain ribosomal RNA genes.' NORs are easily demonstrated by the so-called argyrophilic nucleolar organizer region Abbreviations: NOR, nucleolar organizer region; AgNOR, argyrophihc nucleolar organizer region; HCC, hepatocellular carcinoma; UICC, International Union Against Cancer; AFP, alpha-fetoprotein.