Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and also shown to be associated with the development of esophageal and lung cancers. To determine if these genes are also involved in the development of gastric cancer, 79 primary human gastric cancers were examined for loss of heterozygosity of APC or MCC or both. Loss of APC was detected in 20% of 15 informative differentiated cases, but not in 20 informative undifferentiated cases, while loss of MCC occurred in 23.5% of 17 informative undifferentiated cases, but not in 19 informative differentiated cases. These data suggest that loss of heterozygosity of APC/MCC gene is involved in the development of gastric carcinomas, and that distinctly different molecular mechanism(s) may be responsible for the development of differentiated and undifferentiated gastric carcinomas.