As a first step toward understanding molecular mechanisms in human pancreatic carcinogenesis, we attempted to search for the location of tumor suppressor genes by examining loss of heterozygosity (LOH). Frequent LOH was observed in six chromosomal regions: in chromosome arms 1p, 6q, 9p, 12q, 17p, and 18q. Because chromosome arm 12q is reported to be a target for allelic loss in gastric cancer or male germ cell tumor, we focused further on this region in 66 primary specimens, and identified the minimal common region of allelic loss within a 1-cM interval in 12q22-q23.1. Microsatellite instability (MI) was also examined in this study, and the incidence of MI(+) cases, in which MI of two or more microsatellite loci was detected, was 61%. In tumors with MI(+), we further surveyed for somatic mutations in the transforming growth factor beta receptor type II (RII) gene and found no mutation in pancreatic cancer. Our results in the present study help to shed light on the understanding of pancreatic carcinogenesis.