Precancerous polyposes other than classic familial adenomatous polyposis and the condition hereditary nonpolyposis colorectal cancer, or Lynch syndrome, continue to present major diagnostic challenges for the anatomic pathologist. This editorial highlights the practical significance of novel insights and clinical guidelines in the recent literature, as well as in 4 contributions to this edition of the Archives of Pathology & Laboratory Medicine. The first section will address attenuated familial adenomatous polyposis and a newly recognized type of autosomal-recessive adenomatous polyposis associated with the DNA repair gene MYH. The remainder of the editorial discusses the role of the revised Bethesda guidelines in the diagnosis of hereditary nonpolyposis colorectal cancer and concludes with the recently identified serrated pathway syndrome.