Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K-ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K-ras. No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K-ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.