Purpose For many decades, endometrial cancer (EC) has been considered as a homogenous tumor entity with good prognosis. The currently valid risk stratification considers clinical and pathological factors. Treatment recommendations differ considerably from country to country. Materials and methods The Cancer Genome Atlas (TCGA) Research Network has shown that ECs should be reclassified into four novel molecular prognostic groups, with the potential of changing adjuvant management of EC patients: ultra-mutated, hyper-mutated, copy-number low, and copy-number high. Clinical examples are shown, and the available literature has been highlighted. The European Society of Gynaecological Oncology (ESGO) guideline for endometrial cancer takes the new classification system into consideration for adjuvant treatment decisions and will be published this year. Results In the near future, we expect new treatment recommendations that may differ considerably from the clinicopathologically driven recommendations on the basis of our deeper insight and better understanding of molecular markers in endometrial cancer. The PORTEC 4a study is the only recruiting study which randomizes patients to adjuvant or no adjuvant treatment on the basis of the aforementioned new classification system. Conclusion The aim of the new classification is a more personalized adjuvant radio(chemo)therapy decision and better oncologic outcomes or avoidance of overtreatment
