Massive gastric tumors may be inseparable from the splenic hilum, distal pancreas, splenic flexure of the colon, or the fourth portion of the duodenum. In patients with large GISTs, neoadjuvant imatinib mesylate is highly recommended as it may reduce the extent of the operation required to remove the tumor. Generally, we perform a computed tomography (CT) 2–4 weeks after starting imatinib to check for tumor response, which can be detected by a decrease in tumor perfusion and density. Size is not a reliable indicator of response initially, because a responsive tumor may not decrease in size and occasionally may even swell temporarily. Therefore, it is important that the surgeon personally review the radiologic films. In the absence of tumor progression, imatinib is then continued and scans are repeated 3 and 6 months later. Generally, resection is attempted between 6 and 9 months following the start of a tyrosine kinase inhibitor. Rarely, a total gastrectomy is required to remove adequately a proximal gastric GIST, especially if it is large. This possibility should be discussed with the patient preoperatively.