Spontaneous tumor lysis syndrome (TLS) is a rare condition in solid tumors, particularly in endometrial carcinoma. Spontaneous TLS occurs without the use of cytotoxic therapy but is observed particularly in hematologic malignancies. Given the high morbidity and mortality associated with spontaneous TLS, it is crucial to identify and treat it promptly. There have been only four cases of spontaneous TLS reported to date in the literature from a uterine source. We present a 59-year-old female with a recently diagnosed endometrial carcinoma with neuroendocrine features by dilation and curettage who presented to the hospital with somnolence, decreased oral intake, and lower abdominal pain of three days duration. She was found to have sepsis secondary to endometritis and spontaneous tumor lysis syndrome by clinical and laboratory definitions (hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia). Signs of disease progression were found such as worsening retroperitoneal lymphadenopathy that corresponded with the suspected increased tumoral activity. We report the case of a solid tumor (endometrial) presenting with spontaneous TLS, which highlights the importance of the early identification and initiation of treatment.