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ABSTRACT AimWe investigated the biogeographic consequences of chromosomal speciation, or structural changes in chromosome arrangement that lead to reproductive isolation, an intriguing speciation mechanism with implications for the phylogenetic and geographic distribution of species and chromosomal diversity. Location. North and Central America. Taxa. A species‐rich and chromosomally diverse clade of lizards in the genusSceloporuswhich are known to have coincident bursts of speciation and karyotype diversity, and coincident patterns of chromosomal change and branching order. Some workers have suggested that the tendency of communities ofSceloporuslizards to include species with different karyotypes is a signal of widespread chromosomal speciation, but given the high karyotypic diversity present inSceloporus, this may be due to chance rather than the effects of karyotypic speciation. MethodsWe gathered karyotypic, morphological, and biogeographic data on this chromosomally‐diverse clade in order to assess whether sympatry patterns ofSceloporusspecies are structured by karyotype. If karyotypic rearrangements contribute to the creation or maintenance of new species inSceloporus, then sympatric sister taxa should be more karyotypically diverged than allopatric sister taxa, and allopatric taxa should accumulate differences more gradually. We investigate whether species pairs with similar karyotypes are less likely to overlap geographically than expected by chance, and test whether karyotypic and geographic overlap between species pairs is related to divergence time. We pay special attention to cases of overlap between sister species. We also investigate whetherSceloporuscommunities are karyotypically overdispersed by comparing observed geographic distributions of karyotypic and phylogenetic diversity against phylogenetically‐informed modeled distributions. ResultsWe find little evidence for geographic signatures of chromosomal speciation and suggest that, while chromosomal speciation may have contributed historically to the spatial distributions ofSceloporusspecies, any geographic signature of this mode of speciation has been lost at long (> 10 Ma) temporal and broad (continental) spatial scales. Main ConclusionsThe spatial signature of chromosomal speciation is temporally restricted and the influences of other factors may have greater effects on species distributions over long time scales in this group.