Objective To study the diagnostic value of radial echoendoscopy combined with ultrasonic micro-probe for differentiating mediastinal disease from esophageal submucosal lesion. Methods Data of 53 patients with esophageal eminence with unknown origin detected by gastroscopy or CT in China-Japan Union Hospital were reviewed. Ultrasonic micro-probe was performed first and followed with radial echoendoscopy. The diagnosis was compared with the results of CT. Results The diagnostic sensitivities of EUS and CT for esophageal submucosal lesion were 90. 9% （20/22） and 50.0% （11/22 ）, and the specificities were 93.5% （29/31 ）and 83.9% （26/31 ）. The sensitivities for the benign mediastinal disease were 91.7 % （22/24） and 70. 8% （17/24）, and the specificities for the benign disease were 93.1% （27/29）and 62. 1% （18/29）. The sensitivity and specificity for malignant mediastinal disease were both 100. 0%. Conclusion Radial echoendoscopy combined with ultrasonic micro-probe shows prominent advantage in the diagnosis of the esophageal submucosal lesion and mediastinal disease over CT, especially in the specificity and sensitivi- ty for esophageal submucosal lesion and benign mediastinal disease.