Undifferentiated osteoclast-like giant cell carcinomas (UOLGCCs) of the digestive tract are very rare, with only a few cases reported in the literature. An 82-year-old man was referred to the emergency department for melena. Endoscopic examination revealed a hemicircumferential ulcerovegetative lesion, involving the bulbar apex and extending to the second portion of the duodenum; biopsies revealed an UOLGCC. The patient underwent transfusion support therapy, and he was proposed for best supportive care. Duodenal UOLGCC is an extremely rare cause of upper gastrointestinal bleeding. Clinical findings and therapeutic approach represent a challenge in this pathology.