POLE mutation is a prognostic marker associated with excellent outcome in endometrial carcinoma (EC). However, these EC tumors frequently have aggressive histology. The aim of this study was to determine how to integrate the implications of POLE mutations into existing risk assessment strategies and further stratify patients. We detected POLE mutations in a cohort of 426 ECs from Chinese women and observed their prognostic significance in terms of survival and recurrence outcomes in combination with histological and other molecular characteristics, including microcystic, elongated and fragmented (MELF) pattern invasion, histologic subtype, tumor grade, myometrial invasion and p53 protein and mismatch repair protein expression status. POLE mutations were identified in 38 of 426 ECs (8.9%). The most common mutations were P286R (31.6%), V411L (15.8%) and Q453R (15.8%). We confirmed that POLE mutation was associated with improved overall survival (P = .047), although it did not show a statistically significant relationship with progression-free survival (P = .45). Interestingly, further analyses indicated that in POLE-mutant tumors, MELF pattern invasion was associated with a 15.1-fold increase in tumor recurrence or progression risk (HR = 15.1, 95%CI = 1.57-145.3, P = .018), whereas this phenomenon was not present in the POLE-wild-type subgroup (HR = 0.90, 95%CI = 0.39-2.08, P = .80). Furthermore, higher staging and deeper myometrial invasion also showed much higher risk in patients harboring POLE mutations compared with those without POLE mutations. Although POLE mutation was associated with favorable overall survival, the combined consideration of POLE mutation status and established clinicopathologic factors in the risk assessment of endometrial cancer is more accurate than the consideration of clinicopathologic factors alone and might lead to precise and individualized therapeutic strategies. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.