Gastrointestinal stromal tumors account for 0.1-3% of all gastrointestinal neoplasms and are characterized by features that overlap with those of other mesenchymal tumors. We expose the case of a 58-year-old male patient who complained of abdominal pain, weakness and melena. Microscopic examination of surgically resected gastric tumor revealed a neoplastic proliferation composed of spindle cells with eosinophilic cytoplasm, elongated nuclei with rounded ends, palisadic disposition and intracytoplasmic perinuclear vacuoles, low cyto-nuclear polymorphism, mild atypia and mitotic activity of 3-5÷50 HPF. Some histopathological features requested differential diagnosis with schwannoma and tumors of myocytary origin, based on immunohistochemical techniques, which have established a final diagnosis of spindle cell gastric stromal tumor. We also reviewed the GIST-related literature and evaluated the possible methods of preoperative diagnosis of GISTs based on endoscopic biopsy. Proper classification of GISTs based on histopathological criteria and immunohistochemical techniques has a great prognostic and therapeutic utility. Future development of endoscopic biopsy methods will refine the management of gastrointestinal stromal tumors.