INTRODUCTION: Cholestatic hepatitis is a rare manifestation of both solid organ and hematologic malignancies. It has been reported to occur with ovarian cancer, but not other female genitourinary tract malignancies to our knowledge. We report a case of simultaneous cholestatic hepatitis and acute sensorimotor polyneuropathy as paraneoplastic syndromes of endometrial adenocarcinoma. CASE DESCRIPTION/METHODS: A 66-year-old woman with past medical history of newly diagnosed stage IIIC endometrial adenocarcinoma and cholecystectomy presented with ascending bilateral lower extremity weakness and numbness for 14 days. Physical exam revealed bilateral foot drop and distal lower extremity numbness. Patient did not have jaundice or scleral icterus. Laboratory assessment showed ALT 172 U/L (normal < 61 U/L), AST 149 U/L (normal < 40U/L), ALP 243 U/L (normal < 126 U/L), and GGT 461 U/L (normal < 85 U/L). Lumbar puncture showed CSF albuminocytologic disassociation. Further neurologic workup was consistent with an acute sensorimotor polyneuropathy, which was attributed to a paraneoplastic process of her cancer. During investigation of her polyneuropathy, transaminases and ALP continued to rise to peak values of ALT 245 U/L, AST 202 U/L, and ALP 659 U/L so workup of cholestatic hepatitis was pursued. Total bilirubin and INR remained normal. Fractionated ALP showed a majority liver fraction. Infectious, autoimmune, pharmacologic, malignant, metabolic, and drug-induced causes of cholestatic hepatitis were screened for and ruled out. Liver ultrasound with doppler was negative for acute biliary or liver pathology. CT of the chest, abdomen, and pelvis with IV contrast showed a normal liver. Additional workup for cholestatic hepatitis, including liver biopsy, was not pursued as ascending paralysis progressed to paraplegia and patient opted for hospice care. Patient was diagnosed with paraneoplastic, acute cholestatic hepatitis from endometrial adenocarcinoma. DISCUSSION: To our knowledge, this is the first case report of cholestatic hepatitis as a paraneoplastic syndrome of endometrial adenocarcinoma. Our patient’s liver injury may have occurred due to paraneoplastic proinflammatory state or tumor antigen-antibody cross reactivity with liver cell antigens, or a combination of both. Gastroenterologists should include paraneoplastic processes of cancer in the differential diagnosis for liver injury, especially when workup of alternative causes is unrevealing.