Gastrointestinal stromal tumors GISTs are distinctive KIT-positive mesenchymal neoplasms. The genetic alterations leading to the malignant behavior of these tumors are not well characterized. In this study, 21 cases of GISTs (eight low malignant potential, nine primary malignant and four intra-abdominal recurrences) were characterized by immunohistochemistry and evaluated for loss of heterozygosity of the short arm of chromosome 9, using six microsatellite markers. Loss of heterozygosity with at least one microsatellite marker at 9p region was a common finding in high-risk GISTs (malignant and recurrent group) but was absent in the low malignant potential group. Recurrent GISTs showed more frequent deletions than their primary tumors. All cases with loss of heterozygosity showed deletions at 9p21. Similarly, all low malignant potential GISTs were immunoreactive for p16, whereas malignant tumors were negative for p16. These results suggest that loss of p16(INK4A) gene on 9p may contribute to the progression and/or malignant transformation of GISTs.