BACKGROUND/AIMS: As the relationship between gastrointestinal stromal tumors (GIST) and interstitial cells of Cajal had become clear, GIST is defined as CD117 positive mesenchymal tumors, and recognized as a new distinct entity among mesenchymal tumors presenting as gastrointestinal submucosal tumors (SMT). To evaluate GISTs in the category of SMTs, we analyzed mesenchymal SMTs immunohistochemically and clinicopathologically. METHODS: Forty-five patients with mesenchymal SMTs, who received surgical or endoscopic resection were retrospectively analyzed for clinical parameters. Immunohistochemical staining for CD117, CD34, NSE, SMA, and S-100 was also performed. RESULTS: Among 45 tumors, 41 (91.1%) expressed CD117 and were diagnosed as GIST. The most frequent location was the gastric body. Except esophageal location (73.3%), GISTs accounted for 100% of SMTs in the gastrointestinal tract. The mixed myoid-neural differentiated type and the spindle cell shape were most common. Metastasis was observed in 5 patients (11%). All of them had tumors larger than 5 cm and died. Their mean survival was 4.6 months. CONCLUSIONS: GIST accounted for majority (91.1%) of SMTs. The presence of metastasis and tumor size at the time of diagnosis indicate poor prognostic factors. Immunohistochemical study is necessary for exact diagnosis of GIST.