AIM To report on a more accurate diagnostic possibility offered by endoscopic ultrasound-guided cutting of holes and deep biopsy (EUS-CHDB) for pathologic diagnosis of gastric infiltrative tumors and gastrointestinal submucosal tumors. METHODS Ten consecutive patients who were suspected of having gastric invasive tumors or gastrointestinal submucosal tumors underwent EUS-CHDB with a novel vertical diathermic loop. We reviewed their medical data and analysed the effectiveness and safety of this new method. The final diagnosis was based on the surgical pathology or clinical/imaging follow-up. RESULTS EUS-CHDB was performed successfully in all the ten patients. Neither severe haemorrhage nor perforation occurred in any patient. Among the ten patients, there were three cases of gastric linitis plastica, one case of gastric lymphoma, five cases of gastrointestinal stromal tumors (GISTs), and only one case of chronic non-atrophic gastritis. That is, nine (90%) of the cases CONCLUSION EUS-CHDB may be a technically feasible and safe option for patients with gastric infiltrative tumors or gastrointestinal submucosal tumors. EUS-CHDB may be used as a remedial or even preferred biopsy method for submucosal lesions.