In this review, we describe four ‘traditional' tumor markers that have been widely studied as reflections of CRC heterogeneity: microsatellite instability (MSI) or DNA mismatch repair (MMR) deficiency, the CpG island methylator phenotype (CIMP), somatic mutations in BRAF, and somatic mutations in KRAS. The former two attributes (MSI/MMR and CIMP) represent global phenomena across the colorectal tumor genome indicative of genetic dysfunction, whereas the latter two (BRAF and KRAS mutation status) are point mutations that may act as drivers of CRC development. Here, KRAS is linked to neoplasm.