In this study, we first analyzed the frequency, pattern and significance of germline/somatic MBD4 sequence variants in a large series of human hereditary/familial and sporadic CRC patients/tumors, and found that MBD4 frameshift mutations are only detected in tumors (somatic change), whereas missense variants are detected, at lower frequency, in both normal and tumor DNA. This evidence concerns the gene MBD4 and colorectal carcinoma.