Genomic instability is a characteristic of most cancers and it is argued that genomic instability is a driving force for tumorigenesis. Data herein demonstrate that genomic instability, as evidenced by microsatellite instability (MSI) and promoter methylation of DNA mismatch repair genes, is common in individual glands of pre-malignant colorectal lesions and raises interesting questions about the role of MSI in the development of colorectal carcinoma.