Two influential concepts in tissue patterning are Wolpert’s positional information and Turing’s self-organized reaction–diffusion (RD). The latter establishes the patterning of hair and feathers. Here, our morphological, genetic, and functional—by CRISPR-Cas9–mediated gene disruption—characterization of wild-type versus “scaleless” snakes reveals that the near-perfect hexagonal pattern of snake scales is established through interactions between RD in the skin and somitic positional information. First, we show that ventral scale development is guided by hypaxial somites and, second, that ventral scales and epaxial somites guide the sequential RD patterning of the dorsolateral scales. The RD intrinsic length scale evolved to match somite periodicity, ensuring the alignment of ribs and scales, both of which play a critical role in snake locomotion.