AIM: To assess the diagnostic yield and safety of adeep and large biopsy technique under the guidance of endoscopic ultrasound(EUS) for diagnosis of gastric infiltrating tumors with negative malignant endoscopy biopsies.METHODS: From January 2009 to March 2014, 36 patients in whom gastric infiltrating tumors had been diagnosed by EUS received negative results for malignancy after endoscopic biopsies. The deep and large biopsy technique combined bite-on-bite technique with or without endoscopic mucosal resection(EMR) to obtain submucosal tissue from lesions. EUS was used to select the appropriate biopsy sites. If the lesion protruded into the cavity, EMR was performed for removal of the overlying mucosa and then bite-onbite technique was conducted in the resected area to obtain submucosal tissue. If the lesion appeared to be flat or was difficult to lift by injection, the bite-on-bite technique was directly used.RESULTS: Twenty-eight of the 36 patients were treated by EMR followed by bite-on-bite technique, while 8 patients only underwent bite-on-bite technique. Histological results showed 23 of the 36 lesions were poorly differentiated adenocarcinomas, 2 diffuse large B cell lymphomas, 4 mucosa-associated lymphoid tissue-type lymphomas, and 7 undiagnosed. The deep and large biopsy technique provided a definitive and conclusive diagnosis in 29(80.6%) of the 36 patients. The 12 gastric linitis plastica and 6 lymphoma patients received chemotherapy and avoided surgery. Minor oozing of blood in 2 mucosal resection wounds was managed by argon plasma coagulation and in 5 cases after deep biopsies by epinephrine(0.001%). Neither severe hemorrhage nor perforation occurred in any patient.CONCLUSION: The deep and large biopsy technique is superior to ordinary endoscopic biopsy for achieving an accurate diagnosis of gastric infiltrating tumors.This procedure guided by EUS is an effective and safe diagnostic method for gastric infiltrating tumors in which endoscopic biopsy results were negative for malignancy. AIM: To assess the diagnostic yield and safety of adeep and large biopsy technique under the guidance of endoscopic ultrasound (EUS) for diagnosis of gastric infiltrating tumors with negative malignant endoscopy biopsies. METHODS: From January 2009 to March 2014, 36 patients in whom gastric infiltrating tumors had been diagnosed by EUS received negative results for malignancy after endoscopic biopsies. The deep and large biopsy technique combined bite-on-bite technique with or without endoscopic mucosal resection (EMR) to obtain submucosal tissue from lesions. EUS was used to select the appropriate biopsy sites. If the lesion protruded into the cavity, EMR was performed for removal of the overlying mucosa and then bite-onbite technique was conducted in the resected area to obtain submucosal tissue. lift by injection, the bite-on-bite technique was directly used .RESULTS: Twenty-eight of the 36 patients were treated by EMR followed by bi te-on-bite technique, while 8 patients only underwent bite-on-bite technique. Histological results showed 23 of the 36 lesions were poorly differentiated adenocarcinomas, 2 diffuse large B cell lymphomas, 4 mucosa-associated lymphoid tissue-type lymphomas, and The deep and large biopsy technique provided a definitive and conclusive diagnosis in 29 (80.6%) of the 36 patients. The 12 gastric linitis plastica and 6 lymphoma patients received chemotherapy and avoided surgery. Minor oozing of blood in 2 mucosal resection wounds was managed by argon plasma coagulation and in 5 cases after deep biopsies by epinephrine (0.001%). Neither severe hemorrhage nor perforation occurred in any patient. CONCLUSION: The deep and large biopsy technique is superior to ordinary endoscopic biopsy for achieving an accurate diagnosis of gastric infiltrating tumors. This procedure guided by EUS is an effective and safe diagnostic method for gastric infiltrating tumors in which endoscopic biopsy results were negative for malignancy.