Shockingly few transcription factors and cell signaling pathways are utilized to pattern organs and to specify the fate of a seemingly endless variety of unique cell types during animal development. This dichotomy led to the hypothesis that each factor is used in multiple tissues and that a combinatorial code of factors determines cell fate or tissue identity in a unique fashion. Two recent papers describe temporal changes in the interplay between Hox transcription factors, which specify positional identity, and Wnt signaling, which provides spatial information and promotes asymmetric cell division. These changes guide cells through a series of discrete steps, leading to unique fates. Variations between these two studies highlight the diversifying potential of combinatorial regulation, in short, that the pathways through which these molecules interact can vary even between adjacent cells. Shared features include cross-regulatory interactions to redeploy patterning genes in a tissue-specific manner for organogenesis and coregulation of common downstream targets. Identification of additional combinatorial gene targets and elucidation of their underlying molecular mechanisms are important future tasks in developmental biology and the study of evolution.