GISTs represent a specific group of mesenchymal tumors with unpredictable biological features. Approximately 30% of newly diagnosed GIST tumors are malignant or have a high potential for malignancy. Currently, GISTs are routinely identified using histological, immunohistochemical, and molecular genetic assays. However, clinical diagnosis, particularly of small or intramural GISTs, might be difficult. Endoscopic examinations and fused PET/CT imaging are the most useful techniques for imaging and monitoring the disease progression. Surgical treatment is the first-line treatment and the only method that might lead to full remission in patients with primary GISTs. At the present time, there is no consensus on the issues whether to perform resections in patients with positive margins and resections of metastases. Biological therapy with imatinib mesylate is recommended in patients with newly diagnosed, locally advanced, inoperable, or metastasizing gastrointestinal GISTs that express the c-KIT protein. Treatment may reduce a primary tumor to a size small enough for surgical excision. Current research is focused on the development of new therapies for the treatment of advanced disease and/or disease prophylaxis.