Recent advances in molecular biology have unveiled the mechanisms of carcinogenesis, especially colorectal carcinogenesis. A large body of evidence supports the idea that accumulated genetic changes due to inherited as well as environmental factors underlie colorectal cancer development. Recently, several reports have suggested that aberrant methylation of the CpG island may also play an important role in colorectal carcinogenesis. This genetic information is not yet sufficient but some useful genetic information can be applied clinically. This paper presents the results of intensive study of microsatellite instability in colorectal cancers and some clinically applicable discoveries. Future problems are also discussed.