Colonoscopic adenomatous polypectomy has reduced the incidence of colorectal cancer and mortality. However, current data suggest that colonoscopy is not as effective as thought. 9% of patients with colorectal cancer have had a normal colonoscopy for the previous 3 years. The decline in incidence and mortality rates for proximal colon cancer relative to distal colon cancer is not very significant. Several studies have shown that interstage colorectal cancers are more common in the proximal colon and share the same molecular profile as SSA/Ps and serrated colorectal pathways (CIMP-high and MSI-H). Therefore, it is currently believed that SSA/Ps may contribute to a large proportion of “post-colonoscopic cancers” (interstage cancers) in the proximal colon. In addition, approximately 15-20% of CRCs develop from the methylation pathway, suggesting a similar incidence of their associated precursor lesions. The reported low incidence of precursor serrated polyps may reflect the fact that progression from polyp to cancer occurs through a relatively more rapid progression pathway and therefore some interstage lesions are not identified. The recognition of 3 molecular mechanisms of CRC (chromosomal instability, MSI and CIMP) provides molecular tools to identify the respective prodromal lesions. Many studies have shown the same molecular features between benign serrated lesions and CRCs with CIMP-H. Some HPs and most SSA/Ps have BRAF mutations and are CIMP-H, whereas SSA/Ps with cytologic heterogeneous hyperplasia often have MLH1 hypermethylation and MSI of heterogeneous hyperplastic foci. Although some conventional adenomas are also CIMP-H, they are less common than SSA/Ps and conventional adenomas do not have BRAF mutations or MSI. Based on molecular markers and benign serrated lesions Based on the correlation of histologic subtypes and CIMP-H tumors, the HP→SSA/P→SSA/P with cytologic heterogeneous proliferation→carcinoma sequence has been proposed. Recent data suggest that SSA/P with focal conventional (tubular or tubular villous) adenomatous heterogeneous hyperplasia represents progression to carcinoma. Preliminary evidence suggests that a subset of these lesions exhibit inactivation of the mismatch repair gene MLH1 and that regions of heterogeneous hyperplasia often display microsatellite instability. Two large colonoscopic screening studies have confirmed that the ability to detect SSA/Ps is highly dependent on the skill of the endoscopist. hetzel et al. examined the differences between endoscopist polyp detection rates in over 7000 colonoscopies. The detection rates for adenomas, hyperplastic polyps and SSA/Ps were significantly different, with the greatest variation in the detection of SSA/Ps. There was also a significant difference in the ability of pathologists to diagnose SSA/Ps. It is now widely accepted that colonoscopic screening of patients at average risk at age 50 and older should result in a detection rate of adenomas of more than 25% for men and 15% for women. However, there is no recommended minimum detection rate for SSA/Ps, which some studies suggest is 1.5%. Guidelines for periodic post-polypectomy screening in patients with colonic serrated lesions recommend a surveillance interval of 3 years for patients with SSA/Ps ≥10 mm or with heterogeneous hyperplasia and 5 years for patients <10 mm without heterogeneous hyperplasia. If both SSA/Ps and adenomas are present, they should be monitored at the recommended minimum interval. Recent studies have shown the presence of BRAF V600 gene mutations in resected colorectal SSA/Ps, supporting a genetic predisposition, and the mutation is highly associated with serous adenocarcinoma. This evidence coupled with their aggressive phenotype and rapid cancer transformation strongly suggests that patients with these polyps need to be closely monitored, and that not only patients with serrated polyposis syndrome (SPS) but also first-degree relatives of patients with SPS should be closely monitored.