Introduction: This study investigated the incidence, surgical management and outcome of Gastrointestinal Stromal Tumors (GIST) in Upper Egypt. Methods: A retrospective review of all GIST patients admitted a South Egypt Cancer Institute between Jan. 2010 and Dec. 2015 was conducted. Patients' demographics, clinical presentation, tumor characteristics, radiological, pathological and immunohistochemical findings, surgical procedures, recurrence and mortality were recorded. Results: A total of 36 GIST patients were identified, stomach was the most common site (27.8%) followed by the small intestine (19.4%) and the large intestine (16.7%). The mean age at time of diagnosis as 52.8 ± 14.4 (ranged from 17 to 76 years). Of these 36 cases, 20 (55.6%) cases were males and 16 (44.4%) cases were females with a ratio of 1.2:1. About 22 cases (61.1%) presented with primary tumors, eight cases (22.2%) had primary tumors and metastases, three cases (8.35) presented with recurrent mass, whereas one case (2.2%) presented either with recurrent mass and metastases or metastases only. The majority of cases (22) had tumorsize >5 cm. Patients were stratified as high, intermediate, low and very low risk (50.6%, 30.6%, 11.1% and 2.8%, respectively). Almost all the cases were surgically managed and 75% were completely resectable. During follow up (average 26.5 months), 22 patients showed complete recovery, 7 had recurrent or metastatic disease and 2 died due to liver metastasis. Conclusion: The incidence of GIST in Upper Egypt is apparently low. Surgical resection is the preferred choice of treatment. The demographic data of GIST patients in South Egypt Cancer institute were similar to those published in the literature. Other prospective studies are required to assess the prognosis and the effect of treatment.