Such variations have pathological consequences, with the classic “two-colon concept” of colorectal carcinoma describing striking differences in clinical, molecular, and epidemiological features of tumors in the proximal and distal colon [74], and more recent data revealing a gradual increase in the frequency of the CpG island methylator phenotype, microsatellite instability, LINE-1 methylation, as well as BRAF, KRAS, and PIK3CA mutations in tumors along the bowel at different colonic subsites [75]. The gene discussed is BRAF; the disease is colorectal carcinoma.