Between 1983 and 1994, 66 patients with cancer of the ampulla of Vater were studied to identify prognostic factors and determine who might benefit from radical resection. Three patients (4.5 per cent) died after operation. Radical resection including lymphadenectomy resulted in potentially curative (R0) resection in 92 per cent. The rate of nodal positivity increased with tumour diameter. Patients with up to two positive lymph nodes had a more favourable prognosis than other patients (P < 0.001). Median survival time for all patients was 41 months; the 5-year survival rate was 35 per cent. Radical resection and lymphadenectomy should therefore be the treatment of choice for patients with tumours of the ampulla of Vater.