Our objective was to evaluate and highlight the significance of epigastric tenderness in children and adolescents with chest pain. In a 26-months period, patients who were referred for pediatri cardiology evaluation at Shiraz University of Medical Sciences with chief complaint of chest pain were studied. Patients with epigastric tenderness were evaluated endoscopically by gastroenterologist. Patients who had positive findings on endoscopy were appropriately treated. Since there were no serious findings on cardiac evaluation, no other treatment was necessary. The patients were re-evaluated 4 weeks later. Response to therapy was defined as relief of the initial symptoms as well as epigastric tenderness. One hundred thirty-two patients were referred for evaluation of chest pain during this period. Epigastric tenderness was found in 44 (33.3%) of these patients and endoscopy was performed. Endoscopy showed positive findings in 41 (93.2%). Thirty (75%) of these patients had varying degrees of gastritis. Duodenitis was found in six (13.6%) and gasteroduodenitis in five (11.4%). Esophagitis, which was always associated with gastritis, was seen in five (11.4%). Only three (6.8%) had normal endoscopy. Urease test was positive in three (7.3%) of the specimens. Two of the patients did not return for follow up. From the remaining 39 patients who received gastroenterology treatment, resolution of symptoms was seen in 38 (97.4%). Careful history and physical examination must guide the assessment of children and adolescents referred for evaluation of chest pain. Epigastric tenderness must be used as a reliable sign to initiate a gastrointestinal evaluation.