Endometrial cancer is the most common gynecological malignancy in high-income countries and the sixth most common cancer in women. Overall incidence has risen in the last few decades as a consequence of the increase in the prevalence of its risk factors, mainly obesity and the aging of the population, and although diagnoses have increased across all age groups, the incidence rates have doubled in women under the age of 40 years. The survival rates of endometrial cancer are highly dependent on its stage at diagnosis, bringing to the fore the importance of early diagnosis. The aim of a screening strategy in this type of tumor should be to detect the disease in the pre-invasive or early stage (before developing myometrial invasion), which would improve cure rates, reduce the morbidity associated with aggressive treatment and offer uterus-sparing management options for younger women. The ideal screening tool in this scenario would be a minimally invasive, inexpensive and easy-to-perform test or auto-test, which could be implemented in a routine gynecologic checkup of patients at-risk or in the general adult population. In this comprehensive review, we aim to define the populations at higher risk of developing endometrial cancer, to assess the performance of current diagnostic tools when used in a screening setting and to discuss the accuracy of new molecular screening strategies.