Nodal assessment represents an integral part of staging procedure for endometrial cancer. The widespread diffusion of sentinel node mapping determinates a phenomenon of migration from stage I to stage III disease, especially for low-risk endometrial cancer patients. The adoption of sentinel node mapping and pathological ultrastaging increase the detection of low volume disease (i.e., micrometastasis and isolated tumor cells), being low volume disease detected in >30% of patients with positive nodes. The prognostic role of low volume disease is discussed as well as the possible adjuvant strategies for patients diagnosed with micrometastasis and isolated tumor cells. The role of further prospective treatments in endometrial cancer, including molecular and genetic profiling, is critically reviewed.