A rare case of duodenal schwannoma is reported. A 69-year-old man was admitted for evaluation of melena. Endoscopy and hypotonic duodenography showed a submucosal tumor in the third part of the duodenum. Biopsy findings were suggestive of leiomyosarcoma, therefore pancreatoduodenectomy was performed. Hematoxylin-eosin staining of the resected specimen showed interlacing bundles of spindle-shaped cells with palisading nuclei. Immunohistochemical staining showed positivity for S-100 protein and neuron-specific enolase, but desmin was negative, thus a diagnosis of schwannoma was made. Schwannoma is often difficult to distinguish from leiomyogenic tumors by standard staining, but immunohistochemical staining proved useful in this case.