Mutations in the transforming growth factor beta type II receptor (TGFbetaRII), Smad2, and Smad4 genes have been detected in several human cancers. However, there are no reports of mutation analysis of the entire coding regions in these genes in hepatocellular carcinoma, and the roles of these genes in hepatocarcinogenesis remain unknown. We screened 30 hepatocellular carcinomas for mutations of these genes using polymerase chain reaction single-strand conformation polymorphism. We detected no mutations, but did find 3 cases of loss of heterozygosity of chromosome 17p13.1. These results suggest that mutations of the TGFbetaRII, Smad2, and Smad4 genes are rare, and that genetic instability is uncommon in human hepatocellular carcinoma.