Periampullary tumour in two Ethiopian patients are described. The first patient, a 60 year old non-insulin dependent diabetic woman with ampullary adenocarcinoma, presented with symptoms, signs and laboratory results suggestive of obstructive jaundice and iron deficiency anaemia. The second patient, a 40 year old lady with duodenal adenocarcinoma, presented with dyspepsia and weight loss of 15 kilogramme. The clinical presentation, diagnosis, and management of periampullary tumours are discussed with review of the literature.