The traditional understanding of adenomas serving as precursors for a homogeneous group of adenocarcinomas is being assailed from all sides. Clearly, the relationship between precursor lesions and adenocarcinomas with defective DNA mismatch repair is much more complex and appears to include right-sided hyperplastic polyps as precursor lesions in some cases. Additional data will be forthcoming regarding this risk of adenocarcinoma development in right-sided hyperplastic polyps, both through defective DNA mismatch repair and methylation of the MGMT gene. This will likely be accompanied by an attempt to reclassify at least some larger hyperplastic polyps as serrated adenomas either on subtle morphologic or molecular grounds.