We have evaluated the feasibility of the use of neoadjuvant imatinib mesylate in the management of unresectable localized gastrointestinal stromal tumors. In a pilot experience, two patients with unresectable gastrointestinal tumors were treated with neoadjuvant imatinib. Their treatment course and surgical outcomes are described. In both cases, the patient attained sufficient tumor regression to enable complete resection of tumor. We conclude that in the management of unresectable gastrointestinal stromal tumors, neoadjuvant administration of imatinib may facilitate sufficient tumor regression to facilitate subsequent tumor resection with curative intent.