As description of enamel microstructure in mammals is mainly performed through 2D sections, interpretations of its formation and development can be misinterpreted by neglecting the complexity of its 3D arrangement. Through Simulenam, a novel software dedicated to the simulation of enamel prisms, and an updated, integrative model of decussation formation, we managed to transform 2D observations of enamel sections into full 3D representations of hippopotamoid enamel microstructure. This allowed us to reinterpret the 2D morphological characters of these taxa into geometric parameters and put a new light on how they evolved through time, with potential implications on their cellular origins – essential steps for furthering our understanding of enamel. Indeed, we also demonstrated that some of these characters could actually be non-homologous across taxa, and that there is at least two fundamentally different ways to produce enamel prism decussation in mammals.