SummaryDiscrimination between low- and high-grade endometrial carcinomas (ECs) is clinically rele-vant but can be challenging for pathologists, with moderate interobserver agreement. Insulin-like growthfactor-II mRNA-binding protein 3 (IMP3) is an oncofoetal protein that is associated with nonendome-trioid endometrial carcinomas but has been limited studied in endometrioid carcinomas. The aim of thisstudy is to investigate the diagnostic and prognostic value of IMP3 in the discrimination between low- andhigh-grade ECs and its added value to L1CAM. IMP3 and L1CAM expression was assessed in tumorsfrom 378 patients treated for EC at 1 of 9 participating European Network for Individualised Treatmentof Endometrial Cancer centers. IMP3 was expressed in 24.6% of the tumors. In general, IMP3 was morehomogeneously expressed than L1CAM. IMP3 expression was significantly associated with advancedstage, nonendometrioid histology, grade 3 tumors, deep myometrial invasion, lymphovascular space in-vasion, distant recurrences, overall mortality, and disease-related mortality. Simultaneous absence ofIMP3 and L1CAM expression showed the highest accuracy for identifying low-grade carcinomas (areaunder the curve 0.766), whereas simultaneous expression of IMP3 and L1CAM was strongly associatedwith high-grade carcinomas (odds ratio 19.7; 95% confidence interval 9.2-42.2). Even within endome-trioid carcinomas, this combination remained superior to IMP3 and L1CAM alone (odds ratio 8.6; 95%confidence interval 3.4-21.9). In conclusion, IMP3 has good diagnostic value and together withL1CAM represents the optimal combination of diagnostic markers for discrimination between low- andhigh-grade ECs compared to IMP3 and L1CAM alone. Because of the homogenous expression ofIMP3, this marker might be valuable in preoperative biopsies when compared to the more patchyL1CAM expression.