To evaluate the different alteration patterns of the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) gene in hepatocellular carcinoma (HCC), 41 HCCs were screened for homozygous deletion and loss of heterozygosity (LOH) at the M6P/IGF2r gene with a dinucleotide repeat polymorphic marker. Of these, three (8.8%) were heterozygous and LOH was observed in two (66.7%) of these informative cases. Five (14.7%) out of 34 informative cases showed homozygous deletions for the dinucleotide repeat polymorphic marker. The frequent allelic loss and homozygous deletion of the M6P/ IGF2r gene suggest that the M6P/IGF2r gene functions as a tumor suppressor gene in the development of HCC.