Macroscelidid afrotherians and canid carnivorans possess four premolar loci, the first of which is not replaced. Previous work suggests that the first premolar in macroscelidids is a retained deciduous tooth, but in Canis it is a successional tooth with no milk precursor. We tested this contrasting interpretation of first premolar homology with data from ontogenetic anatomy and with area predictions from the inhibitory cascade (IC) model. Our results based on anatomy support previous interpretations that the functional first premolar is a retained deciduous tooth (dp1) with no successor in macroscelidids, and a successional tooth (p1) with no precursor in Canis. Hyracoids are among the few placental mammals that show replacement at the first premolar locus and show less deviation than other taxa of actual from predicted areas across the deciduous and molar toothrow. However, predicted vs. actual tooth areas can depart substantially from one another. At least without a better means of representing tooth size, the inhibitory cascade does not help to distinguish the deciduous from successional first premolar. This observation does not rule out the possibility that factors such as a size-shift within the toothrow (e.g., carnivoran carnassials) help to explain deviations from the inhibitory cascade model.