Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas, or leiomyosarcomas, are now classified as GISTs based on histology, immunohistochemistry, and molecular study. They originate from the stem cells that differentiate toward the pacemaker cell (Interstitial cell of Cajal). Prognostic factors have been identified for GISTs and include tumor size and mitotic rate. Surgery is the standard treatment for resectable GISTs. Metastatic and inoperable GISTs should be considered the medication with tyrosine kinase inhibitor (imatinib mesylate), which inhibits the c-kit receptor. The role of the pathologist in the differential diagnosis of GISTs, as well as in the assessment of the malignant potential of the tumors, is becoming increasingly important in influencing decisions regarding clinical management of GISTs. The present paper reviews the literature of GISTs and emphasizes on the field of the pathologist's work.