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Background: Long-term survival for duodenal adenocarcinoma is inconsistent in the literature, and the biology of duodenal adenocarcinoma is poorly understood., Methods: One institution's experience with duodenal adenocarcinoma from 1984 to 2005 is reviewed. Clinicopathologic data were analyzed, and overall survival was estimated using Kaplan-Meier curves with log-rank test., Results: Of the 52 patients, 35 (67%) underwent potentially curative surgery; 31 survived the postoperative period and were included in the analysis. Of these, the median survival was 34 months (range 6 to 186 months) compared with 13 months (range 1 to 24 months) for those not undergoing curative surgery (P < or = .001). Clinicopathologic factors favoring long-term survival were tumor size >3.5 cm (P < or = .001) and T-stage < or =4 (P = .014)., Conclusions: Clinicopathologic factors important to survival in duodenal cancer are T4 tumor status and tumor size. Interestingly, larger tumors were less likely to be invasive, and patients with these tumors had improved survival. The biology of this cancer is poorly understood; therefore, aggressive resection for all duodenal adenocarcinomas is recommended for all patients medically fit to undergo resection.