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We investigated the clinicopathological and immunohistochemical characteristics, genetic aberrations and prognostic factors in 28 patients with extragastrointestinal stromal tumors (EGISTs) from six centers in South Korea.Immunohistochemistry was performed for c-KIT (CD117), PKC-θ (protein kinase C theta), DOG-1 (discovered on GIST-1), CD34, alpha-smooth muscle actin (α-SMA), vimentin, desmin and S-100 protein. Genetic analyses for the KIT gene (exon 9, 11, 13 and 17) and the platelet-derived growth factor receptor alpha (PDGFRA) gene (exons 12 and 18) were performed by direct sequencing of PCR products. The relationships of various clinicopathological characteristics and outcomes were also examined.Of the tumor samples, 78.6% (22/28) were located in the intra-abdominal cavity including the omentum and mesentery, and 10.7% (3/28) were located in the retroperitoneum. All patients were older than 39 years. The median size of the tumors was 10 cm for the maximum diameter. When first detected, 57.1% of EGISTs were large in size, measuring more than 10 cm. Tumors that were larger than 10 cm were found more frequently among tumors with more than 10 mitoses per 50 high-power fields (HPFs) and this finding was statistically significant (p0.05). Based on immunohistochemical results, the EGISTs were positive for c-KIT in 96.4% (27/28) of samples, PKC-θ in 82.1% (23/28), DOG-1 in 85.7% (24/28), PDGFRA in 82.1% (23/28), CD34 in 67.9% (19/28), vimentin in 100% (28/28), α-SMA in 28.6% (8/28), S-100 protein in 39.3% (11/28) and desmin in 28.6% (8/28). c-KIT, DOG-1 and PKC-θ immunostains were sensitive and specific, but the PDGFRA stain was not specific for EGISTs. c-KIT expression was correlated with DOG-1 expression (p0.05). One c-KIT-negative EGIST was also negative for DOG-1, but positive for PDGFRA and PKC-θ immunostains. Out of all EGISTs, 57.1% had tumor necrosis and most of these were more than 10 cm in size, and had obvious nuclear atypia and high mitotic counts (10/50 HPFs). Overall survival (OS) was correlated with tumor size10 cm, tumor necrosis, obvious nuclear atypia, mitotic counts10/50 HPFs and epithelioid or mixed cell type (p0.05). Eleven EGISTs (44.0%) had mutations in the KIT gene and 6 (24.0%) had mutations in the PDGFRA gene, the most common being missense mutations or deletions affecting exon 11 of the KIT gene (n=9) or exon 18 of the PDGFRA gene (n=6). Three cases showed co-existence of both KIT and PDGFRA gene mutations. There were no mutations of exon 17 of KIT and exon 12 of PDGFRA genes.The c-KIT, PKC-θ and DOG-1 antigens are the most sensitive and specific immunomarkers for confirming EGISTs. PKC-θ and PDGFRA immunostains are helpful markers for c-KIT-negative EGISTs. Survival analyses indicated that tumor size10 cm, mitotic rate10/50 HPFs, tumor necrosis, obvious nuclear atypia, and epithelioid or mixed cell type were significant predictors of survival. We found that the combination of these parameters helped to predict aggressive tumor behavior and may be useful for predicting the prognosis of EGISTs. The majority of gene mutations were identified in exon 11 of the KIT gene or exon 18 of the PDGFRA gene. The pattern of KIT and PDGFRA mutations in EGISTs was essentially similar to the one in GISTs. From the immunohistochemistry and molecular genetics perspective, EGISTs may be a special subtype of GISTs. Both immunohistochemical and molecular evaluation are useful for classifying tumors as EGISTs.