Background: About 10% of pancreatic neuroendocrine tumors (pNETs) are thought to be related to inherited syndromes, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 4 (MEN4), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). Here, we report the prevalence of pathological/likely pathological germline variants (PV/LPV) in 2 cohorts: 1) High-risk and 2) Unselected. Methods: We retrospectively collected clinical data of patients with biopsy proven pNETs seen at MD Anderson Cancer Center (MDACC) and Johns Hopkins Hospital (JHH). Cohort 1 (high risk cohort) included 132 patients seen at MDACC, who underwent germline testing based on high-risk criteria such as early onset, personal or family history of cancer and syndromic features between 2013 -2019. Cohort 2 (unselected cohort) included 106 patients seen at JHH, who underwent germline testing following their diagnosis of pNETs between 2020 to 2022. Results: In the high-risk cohort (n = 132), 33% (n = 44) had PV/LPV, and 17 % (n = 22) had a variant of unknown significance (VUS). Amongst the 132 patients, 35% underwent multigene panel testing, 53% had targeted germline testing and 12% had a physician documented outside test diagnosis. The demographics consisted of 52%(n = 69) females, 67% (n = 88) white, 54%(n = 71) had metastatic disease, 58%(n = 76) underwent surgical resection. WHO grading (n = 77) is as follows G1 (39%), G2 (59%), G3 (2%). In the unselected cohort (n = 106), 21% (n = 22) had PV/LPV, 28 % (n = 30) had a VUS. Of these, 93% of the patients underwent multigene panel testing. The demographics consisted of 42% (n = 44) females, 67% (n = 88) white, 48% (n = 51) had metastatic disease, 60% (n = 64) underwent surgical resection, WHO grading (n = 93) is as follows G1 (37%), G2 (49%), G3 (14%). Conclusions: PV/LPV are prevalent in patients with sporadic pNET irrespective of high-risk features or family history. While in the high-risk patients there is a higher prevalence, we also identified a 21% prevalence of PV/LPV with universal germline testing in the unselected cohort. In both cohorts, we identified a high number of mutations in the DNA repair pathway not previously described, which could affect subsequent therapies and surveillance for patients and their family members. The findings support upfront universal germline testing in all patients with diagnosis of pNETs.