Gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting from an activating mutation of stem cell factor receptor (KIT), and an activating mutation of the homologous platelet-derived growth factor receptor alpha (PDGFRA) kinase. Most GISTs (90%-95%) are KIT-positive. About 5% of GISTs are truly negative for KIT expression. GISTs have been documented to resistant conventional chemotherapeutics. Due to the KIT activation that occurs in the majority of the cases, KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic GISTs. Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase, and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase II and III trials. The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease. Molecular analysis in phase I-II trials revealed significant differences in objective response, progression-free survival, and overall survival between GISTs with different kinase mutations. The aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients. © 2013 Baishideng. All rights reserved.