We describe the generation of two orthotopic murine models for endometrial cancer (EC).The first model is generated from endometrial Hec-1A cancer cells transfected with luciferase and injected directly into the uterus of female mice. This model allows a follow-up with bioluminescence imaging (BLI) along the experiment and generates abdominal dissemination and lymphatic and hematogenous metastases in high percentages, also detectables with BLI. The dissemination pattern of this model imitates the advanced stages of EC in patients, and its molecular profile corresponds to aggressive type 2 EC (p53 positive, hormone receptors negative, high percentage of Ki67 positive cells). The second model is derived from endometrioid human tissue collected from surgical pieces. By injecting this tissue inside the uterine cavity of a mouse we obtain orthotopic growth with pelvic dissemination and lymph node metastasis. The molecular pattern observed in human type 1 endometrioid EC (p53 negative, low Ki67 index, presence of hormone receptors) is conserved after the murine growth in orthotopic tumor and metastases. This model supposes a singular pre-clinical tool to study therapeutic agents, though it mimics clinical and molecular behavior of endometrioid EC, which is the most common histology in the patient.