The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). This evidence concerns the gene POLE and endometrial cancer.