Background: Although the importance of KIT and PDGFRA mutations in the oncogenesis of gastrointestinal stromal tumors (GIST) is well established, their prognostic role remains controversial. The aim of our study was to investigate the impact of KIT and PDGFRA gene mutations on the prognosis of patients with GIST after complete primary tumor resection. Methods: Genomic DNA from tumor tissue from 184 patients with primary GIST was submitted to mutational analysis. Exons 9, 11, 13, and 17 of the KIT gene and exons 12, 18 of the PDGFRA gene were sequenced. In addition to the mutational status, several clinical and pathological parameters were analyzed and correlated to the risk of recurrence and long-term disease-free survival (DFS). Results: Somatic mutations were detected in 162 tumors (88.0%). Age (p=0.019), clinical stage (p<0.001), mitotic count (p<0.001), and tumor size (p=0.009) were of prognostic relevance on both univariate and multivariate analysis. Five-year DFS was 41.9%. While the presence of a KIT or PDGFRA mutation per se was not associated with tumor recurrence and/or disease- free survival, exon 11 deletion and hemizygous mutation status were highly predictive for poor survival (p=0.014 and p=0.0004, respectively). Conclusions: KIT exon 11 deletions and somatic loss of the wild-type KIT identified patients with poor prognosis. Age, clinical stage, tumor size, and mitotic count were standard clinicopathologic features that significantly influenced the prognosis. Mutation type of the mitogen receptor c-kit has a potential for predicting the course of the disease and might contribute to management individualization of GIST patients.