Ischemic colitis is a common disease with a good prognosis; however, complications can occur in the presence of a serious underlying disease. Herein, we present a case report in which characteristic findings on lower gastrointestinal endoscopy led to a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). An 82-year-old woman visited our hospital for chronic heart and renal failure. She had a history of breast cancer, myocardial infarction, and hemorrhoidal fistula and was initially hospitalized for ischemic colitis. Subsequent lower gastrointestinal endoscopy revealed extensive ulcerative lesions in the ascending, transverse, and descending colon. Histopathologically, small vessels exhibited multiple fibrin thrombus formations. Based on histopathological and endoscopic results, the presence of an underlying disease was suspected. Flow cytometric analysis showed that erythrocytes and granulocytes had 5.5 and 86.4% CD55- and CD59-negative cells, respectively. The patient was ultimately diagnosed with PNH and considered severely ill, given the ischemic colitis-induced abdominal pain and the need for red blood cell transfusions (4–6 units per month). Accordingly, the patient was administered ravulizumab. Ischemic enteritis did not relapse following ravulizumab administration, and transfusion dependence improved. If a patient with ischemic colitis presents atypical lower gastrointestinal endoscopic findings, it is important to explore the presence of an underlying disease.