Genetic selection has been used to control transmissible spongiform encephalopathies (TSEs) in sheep populations based on the association between PRNP polymorphisms and resistance to scrapie. In goats even if a protective role has been suggested for several polymorphisms (I142M, H143R, N146D/S, R154H, R211Q, Q222K) by different European studies, a similar, univocal association has not been proved so far. The aim of this paper was to identify target polymorphisms in goats and their potential applicability in a selection plan in Italy. For this purpose, the existing genetic data on modulating resistance to classical and atypical scrapie in goats in this country will be used as starting point. Two Italian case–control studies concluded that the polymorphism at codon 222 (from glutamine to lysine Q/K) is important in influencing the susceptibility of goats to classical scrapie. Moreover, goats are susceptible to an unusual form of scrapie, named Nor98, and the H154 mutation was shown to be statistically associated with this disease in goats in an Italian case–control study. Currently, a strategy based on killing goats carrying the H154 mutation is being applied to manage atypical scrapie outbreaks in Italy. The current situation in Italy bodes well for the applicability of breeding plans based on the K222 mutation; data from independent studies on the role of K222 as a protective or even a resistance factor and its frequency in several Italian breeds are available. In the near future, as new data on K222 will be reported, testing the application of selective culling in classical scrapie goat outbreaks may become feasible.