Previous studies suggest that psychological and genetic factors have the potential to explain variability in the musculoskeletal pain experience. There are limited studies simultaneously considering both of these factors in clinically relevant musculoskeletal pain phenotypes. Our purpose was to determine if pain catastrophizing and COMT genotype contributed to clinical or evoked pain sensitivity for subjects with shoulder pain. Our a priori hypothesis was that we would detect a statistical interaction, such that subjects with high pain catastrophizing and a “high pain sensitive” COMT genotype would have the highest pain sensitivity. 58 subjects seeking shoulder surgery were recruited from medical clinics at the University of Florida during a 1-year period. Pre-operatively, subjects completed the Pain Catastrophizing Scale (PCS) and COMT genotype was determined by PCR-based strategies. Subjects also underwent a standard pain assessment that included measures of clinical (numerical rating scale) and evoked (pressure and thermal) pain of the involved shoulder. Separate, between group 2x2 ANOVA models investigated the contributions of pain catastrophizing and previously described haplotypes for COMT pain sensitivity for each of the pain measures. Statistically significant interactions were detected for clinical pain ratings (p = 0.021), thermal pain threshold (p = 0.027) and tolerance (p = 0.010), but not for pressure pain (p = 0.235). The interactions were generally consistent with our hypothesis, indicating that the highest pain sensitivity was associated with subjects having higher amounts of pain catastrophizing and “high pain sensitive” COMT haplotypes. In conclusion, this study provided preliminary evidence that specific psychological and genetic factors have the potential to influence shoulder pain sensitivity.