Purpose: In gastro-intestinal stromal tumors (GIST), loss of heterozygosity (LOH) on chromosome 22 has been described. The prognostic value of these and other DNA regions for patient survival remain unclear. Experimental Design: 60 patients who underwent surgery at our institution between 1992 and 2003 were histopathologically re-classified by immunohistochemistry and the GIST consensus group criteria 2001. 23 microsatellite loci on chromosomes 3, 9, 13, 17, 18 and 22 were screened for alterations in tumor and healthy DNA. Survival was calculated by Kaplan-Meier plots. Results: 11/60 patients showed metastases at presentation (18.3%). 13/60 (21.7%) were high-risk GIST. LOH were found in all tumors. 28/60 (46.7%) showed more than 2 LOH in 23 microsatellite marker sites. The frequency of single marker LOH varied from 1.7% to 28.3% among tumors. Frequent LOH were found on chromosome 22 and 17. The correlation of LOH positivity and the consensus scoring was significant (p<0.001, chi-square test). After a median observation time of 33.3 months (95% confidence interval: 23.9-42.6), overall survival was best for very low, low and intermediate risk tumors with only 6/36 death events, whereas 14/24 high risk and metastasized patients had died (p<0.001, log-rank test). Likewise, LOH significantly predicted survival (p=0.014) and the effect was particularly detrimental for LOH on chromosome 17 (p<0.001). Conclusions: LOH are useful phenomena for the prognosis of GIST. Rather than chromosome 22 markers, chromosome 17 markers independently predict survival. From its linkage to chromosome 17, a fundamental role of p53 in the late stages of GIST can be derived.