Scrapie in sheep is an infectious disease with genetic susceptibility playing an important role. The European Union applied genetics to control scrapie in the sheep population. In goats no clear association between PrP genotypes and resistance to scrapie has been demonstrated yet. Beside investigating this further, it is important to know the PrP genotype distribution in goat breeds. Actually, to estimate the frequency of interesting alleles in a population is a necessary preliminary step to understand how feasible it could be to select them. Aim of this work is to analyse the variability of the PrP gene in goat breeds from a Northern and a Southern Italian regions.Blood samples were collected from 300 goats of the four most common goat breeds reared in Piedmont region, belonging to 81 herds, and from 178 goats of 7 breeds from Basilicata, belonging to 19 herds. PrP gene polymorphisms were detected by direct DNA sequencing on both strands of the PCR products.In total, thirteen point mutations were identified: G37V, T110P, G127S, M137I, I142M, I142T, H143R, R154H, P168Q, T194P, R211Q, Q222K and S240P (the substitutions I142T and T194P are novel). This variability gave rise to 14 alleles. The allele with S127 mutation and the allele with Q211 mutation were found only in Northern goats while V37, I137, T142, R143 and P194 alleles were detected only in Southern goats.Regarding the alleles that were present in both groups, the M142 allele was statistically associated with Northern goats (χ2=39.84, p-value=<0.001) while K222 and H154 alleles were significantly associated with breeds from the South (χ2=54.75, p-value=<0.001; χ2=5.68, p-value=<0.05, respectively). The substitutions T110P, M137I, I142T, P168Q, and T194P were found at a low rate in both Southern and Northern goats and no statistically significant differences were observed between the groups.The present study revealed a high variability in the caprine PrP gene and clear frequency differences between Northern and Southern breeds, with mutations exclusively or significantly associated with one group or the other. M142 and K222 are known to be related to protection against scrapie in goats. More case-control studies are necessary to confirm the protective role of these variants; in fact if this role is confirmed it will allow the introduction of breeding programme to select for resistance to TSEs also in goats.