OBJECTIVES: Gastrointestinal stromal tumors (GIST) is the relatively new term for gastric and intestinal smooth muscle tumors arising from mesenchymal or connective tissue. Knowledge of the epidemiologic, health-related quality of life (HRQL), and economic burden of GIST is important from payer, provider, and patient perspectives and may help guide coverage and treatment decisions for treatments recently available. METHODS: PubMed and six scientific meeting databases were searched for studies of GIST and epidemiology, HRQL, or economics. Relevant publications were assessed as to whether they provided original empirical research. RESULTS: Eleven publications met the review criteria: eight provided data on GIST incidence, and one each on prevalence, HRQL, and cost. Incident cases were identified by medical record review or through extant databases with prospective confirmation by immunohistochemical staining in six studies. The annualized incidence of GIST (cases per million) was: United States (U.S.) (6.8), Iceland (11.0), Netherlands (12.7), Italy (13), Taiwan (13.7) Sweden (14.5), Finland (10 - 20), and France (20.4). Prevalence was estimated at 129 cases per million in Sweden. On the Functional Illness of Chronic Therapy-fatigue instrument, GIST patients scored 40.0 compared to 23.9, 37.6, and 43.6 in anemic cancer, non-anemic cancer, and the general population, respectively (0 = worst; 52 = least fatigue). Ten-year total per patient costs (drug, monitoring, physician visits, adverse events) for managing GIST patients with molecularly targeted treatment were estimated at £47,086 - £ 70,811 compared to £3674 - £ 4230 with best supportive care. CONCLUSIONS: Data suggest the incidence of GIST is similar across countries; lower incidence in one study is likely explained by differences in method of case ascertainment. Although patients with GIST present with fatigue comparable to other cancers, additional research is needed to comprehensively understand its HRQL burden. The increased cost associated with new therapies must be balanced against their expected benefits.