Abstract: Objective: To summarize our experience of diagnosis and treatment of 64 patients with primary malig-nant tumor of the duodenum. Methods: We retrospectively analyzed the clinical data from 64 patients with primary duo-denal malignancy seen in our hospital from 1995 to 2006. Results: Clinical manifestations included jaundice, epigastricdiscomfort, abdominal pain, obstruction of the upper alimentary tract, weight loss and bleeding. It was 2 months before thefinal diagnosis was defined. The misdiagnosis rate was 26.6%. The correct diagnostic rate was 80.8% with duodenal en-doscopy, 75.0% with upper gastrointestinal radiography, 72.5% with CT and 37.8% with BUS, respectively. There were 62cases who underwent surgery with a resection rate of 58.1%. Most primary malignant neoplasms (78.1%) were located inthe second portion of duodenum and the most common pathology type was adenocarcinoma. The overall 1-year and 5-yearsurvival was 61.8% and 34.4%, respectively. The median survival period was 20.2 months. The 5-year survival was 47.7%in patients with radical procedure and 19.1% in patients with palliative procedure(P=0.001). The recurrence rate after rad-ical surgery was 30.6%. Hepatic metastasis was the main cause of failure of the treatment. Conclusion: Primary malignan-cies of duodenum are difficult to be diagnosed early and the misdiagnosis rate is high. Duodenal endoscopy and upper gas-trointestinal radiography are effective tools for the diagnosis of primary duodenal neoplasms. Surgery is the primary treat-ment and should be based on the histological type, location, and size of the tumor. Postoperative adjuvant therapy is alsohelpful.