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The purpose of this study was to evaluate whether ampullectomy can substitute for pancreatoduodenectomy (PD) in early ampullary cancer by clinicopathologic study.Although ampullectomy has been attempted in early ampullary cancer (pTis, pT1), the indication and extent of resection have not been established.Of 201 patients who had undergone PD for ampullary cancer between 1986 and 2002, 67 patients with a histologic diagnosis of pTis (n = 5) or pT1 (n = 62) cancer were analyzed retrospectively. Pathologic PD specimens were reviewed to analyze the cancer spread pattern, and medical records were reviewed for clinical outcomes.The 5-year survival rate of the 66 patients with early ampullary cancer (excluding one mortality) was 83.7%. Recurrence was confirmed in 12 patients (18.2%) and all died because of the recurrence. Pathologic review showed that 22 patients (32.8%) had at least one risk factor for failure after ampullectomy: lymph node metastasis (n = 6, 9.0%), perineural invasion (n = 1), or mucosal tumor infiltration along the CBD or P-duct (n = 15, 22.4%). Mean lengths of invasion into the CBD or the P-duct beyond the sphincter of Oddi were 7.7 mm (range, 1–25 mm) or 6.3 mm (range, 2–18 mm), respectively. Moreover, these risk factors were not correlated with tumor size, histologic grade, or the gross morphology of the primary tumor, although pTis cancer or pT1 cancer sized 1.0 cm or less was found to be least associated with risk factors.Ampullectomy for early ampullary cancer should not be considered an alternative operation to PD because of the high possibility of recurrence. PD should be preferably performed for adequate radical resection, even in early ampullary cancer, and ampullectomy should be reserved for those who have pTis or pT1 cancer sized 1.0 cm or less with high operative risk.