As mentioned before, key molecular events for the development of invasive lesions of the intestine, such as chromosomal instability (CIN), microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and mutations in driver genes such as APC, KRAS, TP53, PIK3CA, and SMAD4, are present in the development of sporadic CRC as well as inflammation-driven CRC. The gene discussed is SMAD4; the disease is colorectal carcinoma.