The Persian cat is mainly characterized by an extremely brachycephalic face as part of the standard body conformation. Despite the popularity, world-wide distribution, and economic importance of the Persian cat as a fancy breed, little is known about the genetics of their hallmark morphology, brachycephaly. Over 800 cats from different breeds including Persian, non-Persian breeds (Abyssinian, Cornish Rex, Bengal, La Perm, Norwegian Forest, Maine Coon, Manx, Oriental, and Siamese), and Persian-derived breeds (British Shorthair, Scottish Fold, Selkirk Rex) were genotyped with the Illumina 63 K feline DNA array. The experimental strategy was composed of three main steps: (i) the Persian dataset was screened for runs of homozygosity to find and select highly homozygous regions; (ii) selected Persian homozygous regions were evaluated for the difference of homozygosity between Persians and those considered non-Persian breeds, and, (iii) the Persian homozygous regions most divergent from the non-Persian breeds were investigated by haplotype analysis in the Persian-derived breeds. Four regions with high homozygosity (H > 0.7) were detected, each with an average length of 1 Mb. Three regions can be considered unique to the Persian breed, with a less conservative haplotype pattern in the Persian-derived breeds. Moreover, two genes, CHL1 and CNTN6 known to determine face shape modification in humans, reside in one of the identified regions and therefore are positional candidates for the brachycephalic face in Persians. In total, the homozygous regions contained several neuronal genes that could be involved in the Persian cat behavior and can provide new insights into cat domestication.