Disruption of the DNA mismatch repair system, characterized by microsatellite instability (MSI), plays an important role in the course of human carcinogenesis. Frequent somatic mutations in a polyadenine (poly(A)) tract and two GT repeats within the coding region of the transforming growth factor beta (TGFbeta) receptor II (RII) gene were reported in colorectal cancers with MSI. We examined mutations of RII in cancers of various organs with MSI and found deletions at the poly(A) tract in eight of nine (89%) gastric cancers and four of five (80%) colorectal cancers. In contrast, no mutations were found in cancers of the pancreas, endometrium, or lungs. These results suggest that TGFbeta-mediated growth control plays a very important role in the stomach and colorectum.