We examined tissue extracted from 19 gastric, 7 pancreatic, and 23 colorectal carcinoma specimens to determine the comparative incidence of allele loss on chromosomes 5, 17, and 18 and that of KRAS2 point mutations. Chromosome 5 allele loss occurred at the same frequency in all three gastrointestinal tumors (approximately 30%), whereas chromosome 17 and 18 allele losses were seen at a significantly lower frequency in gastric (20%) and pancreatic (0%) malignancies than in colorectal cancer (57%). Point mutations in KRAS2 were seen in 83% of pancreatic and 52% of colon cancers, but not in gastric cancer specimens. In pancreatic tumors, these mutations were always found in the second nucleotide of codon 12. In colorectal cancer, the distribution was more variable, involving the second nucleotide of codon 13 and both the first and second nucleotides of codon 12. These results suggest that inactivation of the adenomatous polyposis coli gene on chromosome 5 may be an initiating step for carcinomas of the stomach and pancreas as well as of the colon, but that the genes involved in tumor progression events may be tissue- or tumor-specific.