SUMMARY To assess the ability of protein-coding mutations to contribute to subtle, inter-specific morphologic evolution, here, we test the hypothesis that mutations within the protein-coding region of runt-related transcription factor 2 (Runx2) have played a role in facial evolution in 30 species from a naturally evolving group, the mammalian order Carnivora. Consistent with this hypothesis, we find significant correlations between changes in Runx2 glutamine–alanine tandem-repeat ratio, and both Runx2 transcriptional activity and carnivoran facial length. Furthermore, we identify a potential evolutionary mechanism for the correlation between Runx2 tandem repeat ratio and facial length. Specifically, our results are consistent with the Runx2 tandem repeat system providing a flexible genetic mechanism to rapidly change the timing of ossification. These heterochronic changes, in turn, potentially act on existing allometric variation in carnivoran facial length to generate the disparity in adult facial lengths observed among carnivoran species. Our results suggest that despite potentially great pleiotropic effects, changes to the protein-coding regions of genes such as Runx2 do occur and have the potential to affect subtle morphologic evolution across a diverse array of species in naturally evolving lineages.