Epidermal growth factor receptor (EGFR) plays an important role in cancer biology and offers a promising molecular therapeutic target. The expression profile of EGFR in gastrointestinal stromal tumors (GISTs) is derived from a limited number of small series samples and case reports. We evaluated the involvement of EGFR in human gastric GISTs. Tissue microarray sections representing 33 gastric GISTs with known follow-up were surveyed by immunohistochemistry, using antibodies specific for EGFR. Expression of EGFR was identified in 8/33 (24.2%) cases, and tended to be present in tumors of smaller size (3.69+/-0.66 cm vs. 10.69+/-1.52 cm, P=0.0001), fewer mitoses (3.5+/-1.0/50 high power field vs. 23.44+/-7.61, P=0.0073), and lower necrosis percentages (0% vs. 5.37+/-1.37%, P=0.0003); the expression was more frequently seen in the benign/probably benign category (6/8, 75%, P=0.047), than in gastric GISTs that lacked EGFR expression. Expression showed a trend as a favorable prognostic indicator but did not reach statistical significance, although the number of cases was limited. This observation suggests that EGFR is present in some gastric GISTs, especially in small tumors, and might participate in the growth regulation of human gastric GISTs. Expression of EGFR in some gastric GISTs might be of clinical significance with the recent emergence of EGFR-targeted therapies.