POLE and Leigh syndrome: In the context of LS, EC may display a wide range of histologic morphologies and is most tightly associated with mutations in MSH2 and MSH6. In the clinic, we may use MMR IHC, MLH1 promotor hypermethylation, MMR germline testing, MSI, somatic and or germline POLD1 and POLE screening, and somatic MMR testing in all patients with newly diagnosed EC to identify sporadic endometrial cancer, LS, or Lynch‐like syndrome.