The 2021 edition of the WHO Guidelines will again combine “molecularly defined” and “histologically defined” tumor features, defining four molecular subgroups (WNT-activated, SHH-activated and TP53-wildtype, SHH-activated and TP53-mutant, and non-WNT/non-SHH) and retaining the same four histological groups, while now considering them as “patterns” [7]. The gene discussed is SHH; the disease is neoplasm.