The effect of the stearoyl-CoA desaturase (SCD) and sterol regulatory binding transcription factor 1 (SREBF1) polymorphisms on the volatile compound profile of dry-cured hams from Italian protected denomination of origin (Prosciutto di Parma, Prosciutto di San Daniele and Prosciutto Toscano) was investigated by proton transfer reaction time-of-flight mass spectrometry. The SCD polymorphism had a strong effect on the volatile compound profile in Prosciutto di San Daniele, but moderate in Prosciutto di Parma and very scarce in Prosciutto Toscano. Moreover, the effect of the SREBF1 polymorphism was also strong in Prosciutto di San Daniele and moderate in Prosciutto di Parma and Prosciutto Toscano. The main effect of both markers was found in the peaks tentatively identified as volatile compounds from the unsaturated fatty acids oxidation, with higher concentrations in dry-cured hams with SCD TC and SREBF1 AG genotypes, as they seem to increase the concentration of the fatty acids precursor of those compounds