Our study identifies, for the first time, SATB2 and GATA3 expression as features of Hyams’ grades 1–3 ONBs, expands the spectrum of SATB2 and GATA3-positive neoplasms, and suggests that Hyams’ grade 4 ONBs are not only clinically but also biologically different from low graded ONBs. This evidence concerns the gene SATB2 and neoplasm.