BACKGROUND/AIMS: Risk assessment by mitotic count in the gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm, is important. EUS-guided fine- needle aspiration cannot obtain sufficient tissue for determination of mitotic count, but An EUS-guided Tru-Cut biopsy (EUS-TCB) can. The aim of this study was to evaluate clinical role of EUS-TCB in differential diagnosis of mesenchymal neoplasm and risk assessment of GIST. METHODS: We prospectively enrolled 18 patients who were diagnosed with submucosal hypoechoic tumors, 2~5 cm, in the muscular layer by EUS in Seoul National University Hospital from November, 2005, to July, 2007. The rates of adequate biopsy and possibility of risk assessment were evaluated. RESULTS: EUS-TCB was performed in 16 patients. The median tumor size was 2.7 cm, and adequate diagnosis was possible in 8 patients. Tumor size in the adequate specimen group was larger than in the inadequate group (p=0.021). The number of needle passes was higher in the adequate specimen group (p=0.012). Risk assessment by mitotic count was possible in only one case. CONCLUSIONS: EUS-TCB in the diagnosis and risk assessment of GIST was inadequate, in part because of insufficient operator experience and small tumors. Development of a new instrument is needed to obtain sufficient tissue.