Factors affecting natural history of gastrinoma (Zollinger-Ellison Syndrome) are not yet entirely understood, although much valid information has been gained in the last two decades. Prognostic factors are: a) adequate reduction of gastric acid overproduction insuring symptomatic control and healing of ulcerative lesions; b) inclusion in multiple endocrine neoplasia-1 syndrome rendering gastrinoma surgery rarely indicated and scarcely efficacious; c) size location and spread of the tumoural process(es) conditioning resectability and risk of metachronous liver and extra-abdominal metastases; d) hepatic and bone metastases, major determinants of death; e) development of paraneoplastic Cushing rapidly out of control and causing death within a short period of time; f) development of fundic EC-Lomas in Zollinger-Ellison Syndrome-multiple endocrine neoplasia-1 patients, generally undergoing benign course but possibly leading to lymph node and (exceptionally) to liver metastases and, sometimes, to total gastrectomy; g) experience of medical and surgical teams which are also most important in order to achieve no operative mortality and minimal post-operative complications.