Background: Gastrointestinal tumors (GISTs) have attained significance in recent years because of their dramatic response to imatinib. Imatinib acts by inhibiting the proliferation and inducing apoptosis of GIST cells which express by activating c-kit mutation. GISTs with activating c-kit mutation show positivity for CD117 marker immunohistochemically. In this study, we analyzed the mesenchymal tumors of gastrointestinal tract morphologically and immunohistochemically. Materials And Methods: In this single-institutional retrospective study from January 1995 to April 2010, 52 mesenchymal tumors of gastrointestinal tract were included. Initially they were grouped under smooth muscle and stromal tumors based on their morphology and immunoreactivity for smooth muscle markers. Later on, they were subjected to additional immunostaining by CD117. Based on this, the mesenchymal tumors were reclassified. Results: In our study, the median age was 50 years (range 20–86 years). Stomach was the most common site (n = 13). After CD117 immunostaining, 16 cases which were originally grouped under smooth muscle tumors were reclassified as GISTs. Conclusion: GISTs showing CD117 positivity are the largest group of mesenchymal tumors of gastrointestinal tract. Categorization of tumors as GIST helps to consider the patients for potential imatinib therapy.