In this study, KIT and PDGFRA gene mutations which play a crucial role in biologic behavior and treatment of gastrointestinal stromal tumors that is the most commonly seen mesenchymal tumors in the gastrointestinal system were evaluated in a series of 29 cases. Total genomic DNA extracted from the paraffin embedded tumor tissues of 29 cases were used as template DNA. With designed primers for exons of KIT and PDGFRA genes, target DNA was amplified using optimized PCR techniques. Amplicons were screened for mutation. After screening, the exons suspected of having undergone mutation were subjected to DNA sequencing analysis. In 17 cases, quality and amount of extracted DNA obtained from archival blocks were sufficient. In only 11 cases, all 6 targeted exons could have been amplified efficiently for further applications and mutations were observed in 4 of these 11 patients. In conclusion, we suggest that it would be reasonable to provide screening tests for mutation in exons 9, 11, 13, 17 for KIT gene and exons 12, 14, 18 for PDGFRA gene following the establishment of the diagnosis of GIST. [Turk J Cancer 2009;39(1):11-17]