An 82-year-old man referred to our medical ward because of epistaxis and melena was found to have 12 Bethesda units of factor V inhibitor. He was managed for bleeding with supportive care, followed by corticosteroid therapy. The bleeding completely stopped 1 week after corticosteroid therapy. Medical history revealed dysphagia during the past 6 months and further evaluation brought to light a squamous cell carcinoma (SCC) in the esophagus. This is the first case of an acquired factor V inhibitor developing in a patient with esophageal SCC without any other risk factors such as surgery.