The DNA copy number changes were investigated in 13 malignant, 3 borderline, and 16 benign gastrointestinal stromal tumors (GISTs) by comparative genomic hybridization. A consistent finding was the loss of DNA copy numbers in chromosome 14q. This was detected in 75% of the benign tumors, in 62% of the malignant tumors, and in two out of the three borderline tumors with a minimal overlapping region located to 14q22. Losses of DNA copy numbers were more frequent than gains, with 2-10 changes in malignant GISTs and 1-3 changes in benign tumors. High-level DNA amplifications, detected only in malignant GISTs, were assigned to 3q26-q29 (40%), 5p (30%), and 8q22-24 (40%). Our results indicate that copy number losses in 14q are an early change during oncogenesis of GISTs and suggest the possibility that a new tumor suppressor gene at 14q22 might be involved in the regulation of differentiation or proliferation of such mesenchymal cells.