Site-dependent profiles of chromosome imbalances (CIs) have been reported in gastrointestinal stromal tumors (GISTs). However, the role of specific CIs in association with metastasis is not clear. Methods: Thirteen resected liver metastatic GISTs, including seven from the stomach and six from the small intestine, were analyzed using comparative genomic hybridization (CGH). The CIs associated with metastatic risk were assessed by comparing them with those identified in our previous study of 25 primary GISTs, including 14 from the stomach and 11 from the small intestine. Results: Synchronous detection of liver metastasis was found more often in patients with intestinal than gastric GIST (5/6 vs. 2/7, p = 0.048). When compared with the primary tumors, the CI profile of liver metastases was similar in the intestinal group, but became more complex in the gastric group. Deletions of chromosomes 1p and 15q were very common (> 80%) in primary and metastatic tumors of the intestinal group, and exhibited a trend towards increase in the metastatic tumors of the gastric group. Both groups had a doubling in the frequency of 22q deletion in the liver metastases, which was not significantly different. Other CIs, including 9p deletion, increased significantly in the liver metastases of the gastric group, but not in the intestinal group. Conclusion: Our results, together with clinical findings, indicated a CGH profile associated with the intrinsic aggressiveness of the GISTs. Deletion of 1p and 15q play a critical role in the acquisition of aggressiveness during early GIST development.