The Distal-less (Dll) gene has an ancient evolutionary origin. Chordates have retained duplicated Dll genes; vertebrates have six distinct paralogues (Dlx1 through Dlx6 in mammals) arranged in three cis-linked pairs that are co-expressed. Dlx genes are expressed in a conserved nested pattern that defines a proximal-distal axis in the pharyngeal arch tissue of vertebrates. Dlx5-/- and Dlx6-/- mouse neonates have similar phenotypic variations in the lower jaw and inner ear bones, with the Dlx6-/- phenotype being a less perturbed version of the Dlx5-/- phenotype. Conversely, Dlx5/6-/- double mutants have a homeotic transformation of the lower jaw into a second set of maxillary structures. The combination of expression patterns and null phenotypes has led to the proposal of a “Dlx code” that patterns the craniofacial tissue. However, the nature of this code, whether individual Dlx transcription factors supply unique functions, or whether they make a quantitative contribution to a more generic and shared Dlx function, is not well understood. One prediction of a quantitative model for Dlx function in the pharyngeal arches is the functional equivalency of the proteins encoded by divergent cis-linked Dlx paralogues. To address this aspect of the model, three core functions of Dlx5 and Dlx6 were compared quantitatively: suppression of cell growth, transcription activity and DNA binding affinity. In most respects both proteins behaved very similarly.