Most colorectal cancers (CRCs) are thought to arise in preexisting polyps called adenomas. A second type of colorectal polyp known as a hyperplastic polyp has been regarded as harmless for decades. Patients with hyperplastic polyps are therefore not thought to be at any increased risk of CRC, and best-practice guidelines indicate that these polyps do not require surveillance colonoscopy. Recently, it has become clear that CRC is not a single disease. One type of CRC (30%) shows a chemical alteration in DNA known as methylation, and a proportion of these also show genetic instability at the level of DNA. There is now strong evidence that the hyperplastic polyp is not harmless, but it might serve as the precursor of CRC with DNA methylation and deficient DNA mismatch repair. This novel pathway applies particularly to the subset of hyperplastic polyps that occurs in the proximal colon. If this premise is correct, it would be unsafe to ignore these polyps. There is now a need to define the genetic steps that explain the evolution of CRCs that develop within hyperplastic polyps. At the clinical level, it will be necessary to identify biomarkers for hyperplastic polyps that are especially prone to malignant conversion. Screening can then be targeted more selectively toward patients who are at significantly increased risk of malignant transformation of hyperplastic polyps.