Subclassification of endometrial carcinoma (EC) based on morphologic features alone has been shown to have suboptimal reproducibility, both in regard to biopsy versus hysterectomy findings, as well as interobserver agreement. This restricts the role of morphologic classification of EC as a tool for risk prediction and therefore treatment planning. A diagnostic algorithm based on The Cancer Genome Atlas (TCGA) classification of EC holds promise for improving accuracy in risk prediction. This classifies EC into 4 groups: those harbouring mutations in the exonuclease domain of DNA polymerase epsilon, POLE (POLEmut), those showing a mismatch repair defect, those showing mutations in TP53 (p53abn) and a heterogenous group showing none of these 3 abnormalities (currently termed no specific molecular profile). These groups can be accurately and reproducibly diagnosed on biopsy samples using a limited panel of tests, namely immunohistochemistry for mismatch repair proteins and p53, and testing for POLE exonuclease domain pathogenic variants. In this article we briefly review the biology, testing and interpretation of POLE and mismatch repair defects in EC.