Only two cases of squamous cell carcinoma of the duodenum have been reported in the literature. The author herein reports a case of squamous cell carcinoma of the duodenum. A 75-year-old man was admitted to our hospital because of nausea, vomiting, and weakness. An endoscopic examination revealed a duodenal tumor. The tumor was circumferential elevated one with duodenal obstruction, and located in the descending part near and distal to the ampulla of Vater. Imaging modalities also detected the duodenal tumor, but did not show tumors of other locations including the pancreas. The duodenal tumor was different from ampullary tumor and pancreatic tumor. Six biopsies were obtained from the duodenal tumor. All the six biopsies showed malignant cells arranged in a medullary pattern. The malignant cells showed hyperchromatic nuclei, and mitotic figures were scattered. Keratinization and intercellular bridges were recognized. The pathologic features were interpreted as a squamous cell carcinoma of the duodenum. The carcinoma was pure squamous cell carcinoma without differentiation into adenocarcinoma or endocrine carcinoma. Operation was not possible because of the patient's age and weakness. The patient was treated by chemotherapy and radiation, but he showed a downhill course. Metastases emerged, and he died of systemic metastasis 17 months after the first presentation. Autopsy was not performed.