Surface pitting in sweet cherry (Prunus avium L.) is characterised by depressions development on the skin surface. Pitting damage happens during harvest and postharvest handling and develops during cold storage. This study compared two cultivars with contrasting susceptibility to pitting (Kordia: tolerant; Sweetheart: susceptible) using a LC-MS/MS proteomic approach to identify key metabolic and signalling pathways related to this disorder during ripening and postharvest storage. The variability observed in the principal component analysis was driven by the cultivars suggesting that surface pitting susceptibility is triggered by the inherent differences between cultivars. Proteins involved in anthocyanin biosynthesis were more abundant in Kordia. Moreover, CCR (cinnamoyl-CoA reductase) and FLS (flavonol synthase) proteins showed higher abundance in Sweetheart. An overexpression in enzymes related to the synthesis of abscisic acid (ABA), jasmonic acid (JA) and ethylene were found in Kordia. A higher abundance of sucrose synthase (SUS), UDP-glycosyltransferases (UDP-GT) and polygalacturonase-inhibiting proteins (PGIP) were observed in Kordia, while a higher content of invertase (INV) was observed in Sweetheart. The overexpression of the studied pathways suggests that tolerance to surface pitting could be correlated to one or more of these factors, and susceptibility might be given by the inherent differences in the metabolic processes of each cultivar.