A 43-year-old woman who had received anticoagulant therapy for atrial fibrillation for 2 years was admitted to our hospital with hematemesis. Endoscopy revealed a huge submucosal hematoma in the antrum of the stomach. Repeat endoscopy on day 6 showed that the submucosal hematoma had developed into a giant ulcer. Gastric mucosal biopsy and general examination confirmed a diagnosis of AL amyloidosis due to multiple myeloma. Although patients with cardiac involvement of AL amyloidosis often require anticoagulant therapy, gastrointestinal bleeding may occur. Therefore, the potential benefits of anticoagulation must be carefully weighed against the risk of hemorrhage.