A 53-year-old woman was diagnosed with gastrointestinal stromal tumor (GIST) of the stomach. Computed tomography (CT) revealed a huge mass (12 cm in diameter), likely to invade pancreas and spleen. In the operation field, the tumor was in an unresectable state. The patient was then started on imatinib therapy for 4 months. On follow-up imaging studies, the tumor almost disappeared. We performed total gastrectomy and splenectomy upon which two small-sized residual tumors were found on microscopy. In this paper, we describe a case of clinicopathologic change in unresectable GIST after neoadjuvant imatinib mesylate.