This multicenter retrospective study of clinical outcomes data examined the clinical performance of Integrated Molecular Pathology (IMP) testing of pancreatic cysts, also known as PancraGEN. The performance of IMP was compared to that of the International Consensus Guideline (ICG) criteria used to triage patients into management by surveillance or by surgery. IMP had a higher accuracy at identifying patients with cysts at higher risk of malignancy compared to the accuracy of ICG criteria (90% vs. 52%). While the negative predictive values (NPV) of both IMP and ICG were the same (97% vs. 97%), the positive predictive value (PPV) of IMP was much higher (58%) than that of ICG (21%). Furthermore, when IMP test results were examined in patients who met ICG criteria for surgery, IMP identified many patients with cysts who met surgical criteria who could have benefited from non-surgical management, given the low risk of malignancy identified by IMP. In addition, IMP identified cancers missed by ICG criteria.