These insights into the molecular genetics and epigenetics of CRC development via the two major pathways, which account for the majority of CRC cases, will help refine strategies for early diagnosis and prognosis that can use a range of genetic markers, such as RNF43, ZNRF3, and RSPO fusions, in addition to methylation-based markers, such as CDX2, CDKN2A, and various Wnt regulator genes. Here, RSPO1 is linked to colorectal carcinoma.