Runx3 is one of the three mammalian Runt domain transcription factors comprising the deeply conserved RUNX gene family. While the three proteins recognize the same DNA-motif, the functional overlaps are minor; each Runx has a distinct subset of biological functions. This lack of functional redundancy is the consequence of a tightly regulated spatio/temporal expression of the genes by transcriptional and post-transcriptional control mechanisms. Over the years several groups created Runx3-deficient mouse models. Analysis of these mice revealed various phenotypic features that result from loss of cell autonomous function of Runx3. Here we summarize the phenotypic similarities and dissimilarities between two of the Runx3-deficient mouse strains, discuss the basis of the discrepancies and highlight the crux of the dispute.