The enamel microstructure of the molariform cheek teeth of Vintana sertichi (Gondwanatheria, Mammalia) from the Late Cretaceous of Madagascar retains many of the plesiomorphic characteristics of mammalian prismatic enamel (e.g., single-layered schmelzmuster; non-decussating, small prisms). However, V. sertichi exhibits a relatively derived condition and resembles Lavanify miolaka (Late Cretaceous, Madagascar), Bharattherium bonapartei (Late Cretaceous, India), and an indeterminate sudamericid (Late Cretaceous, Madagascar) in possessing modified radial enamel, consisting of prisms separated by prominent interrow sheets of interprismatic matrix. A second group of gondwanatherians (Ferugliotherium windhauseni, Gondwanatherium patagonicum, Sudamerica ameghinoi, Greniodon sylvaticus), all from the Late Cretaceous and Paleogene of Argentina, retains relatively primitive, ‘normal’ radial enamel, in which the interprismatic matrix anastomoses around the prisms and does not form interrow sheets. The prisms of gondwanatherian molariforms generally become wider from the enamel-dentine junction to the outer enamel surface, dramatically so in Gondwanatherium. Seams are very rare; tubules are more common. Prism decussation has not been found in any gondwanatherian enamel. Gondwanatherian molariforms lack or have only a thin layer of external prismless enamel, although it is thick in the incisors of Sudamerica. Despite their apparent utility in differentiating among gondwanatherian taxa, or gondwanatherians as a whole from other clades, many of the derived characteristics of gondwanatherian enamel microstructure are found in other mammalian groups and may reflect a high degree of homoplasy.