Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the diagnostic accuracy of chromogranin A (CgA), pancreatic polypeptide (PP), and glucagon for pNET in MEN1. Design: This was a diagnostic study. Setting: The study was conducted at Dutch university medical centers from 2008 to 2011, representing 90% of the total Dutch MEN1 population. Patients and Methods: Patients for whom data on tumor markers in combination with the reference standard (ie, radiological imaging) were availablebetween 2008 and 2011 wereincluded. The reference standard for the presence of pNET was pathology or detection on magnetic resonance imaging, computed tomography, or endoscopic ultrasound confirmed on subsequent imaging, irrespective of modality at follow-up. Main Outcome Measures: The area under the receiver-operating characteristic curve (AUC), positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, sensitivity, and specificity were calculated for each marker. Results: For the analysis of PP, CgA, and glucagon, 73, 81, and 94 patients were available, respectively. The AUC for CgA was 0.48 [95% confidence interval (CI) 0.35-0.61] with as ensitivity 0.33 and a specificity 0.73; the AUC for glucagon was 0.58 (95% CI 0.46-0.70) with a sensitivity 0.43 and a specificity 0.73; and the AUC for PP was 0.64 (95% CI 0.50-0.77) with a sensitivity 0.36 and a specificity 0.74. Age, imaging modality, tumor size, and number did not influence the outcomes. Conclusion: The diagnostic accuracy of the tumor markers CgA, PP, and glucagon for pNET in MEN1 is low. Copyright © 2013 by The Endocrine Society.