Our current study shows that SH3BP2 is expressed in primary tumors and cell lines from GIST patients and that SH3BP2 silencing leads to a downregulation of oncogenic KIT and PDGFRA expression and an increase in apoptosis in imatinib‐sensitive and imatinib‐resistant GIST cells. The gene discussed is KIT; the disease is gastrointestinal stromal tumor.