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Background and study aims: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. Patients and methods: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n?=?492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis (?benign?/?statistically indolent? vs. ?statistically higher risk [SHR]?/ ?aggressive?) or an International Consensus Guideline (Sendai 2012) criteria model for ?surveillance? vs. ?surgery.? The Cox proportional hazards model determined hazard ratios for malignancy. Results: Benign and statistically indolent IMP diagnoses had a 97?% probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P??93?% probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P?

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