We conducted surveys of mutant allele frequencies of four cat populations in Arkansas and Tennessee during 2002. Our calculations and analyses support that Southwestern cat populations were relatively more genetically similar to each other than compared to cat populations in other areas of North America. However, the cat population of Fort Smith is slightly different from the other cat populations studied in the Southwestern United States. Although there is a clear significant spatial geographic pattern for many mutant coat allele frequencies in the United States and Canada cat populations (d, l, S, and W), our results revealed that there is not a significant isolation-by-distance model affecting these cat populations. Our data also support the historical migration hypothesis because our calculated allele frequencies were genetically similar to cat populations located in ancestral areas of Europe. Different phenograms, including new European cat genetic profiles, showed that the Southwestern cat populations studied are of a clear British origin. Therefore, migration routes of early Arkansas and Tennessee settlers help explain the similarities of allele frequencies among domestic cat populations.