Abstract Objective To present a study to identify the characteristics of coexisting early gastric cancer (EGC) and benign submucosal lesions, with the aim of reducing the adverse consequences of overdiagnosis and overtreatment. Methods In this retrospective study, we searched the endoscopic databases of three tertiary centers. We screened of patients suspected of early gastric cancer submucosal infiltration by conventional endoscopy and ultimately selected for endoscopic submucosal dissection treatment after endoscopic ultrasonography and magnifying endoscopy with narrow-band imaging examination. Patients with coexisting EGC and benign submucosal lesions in histological sections were included. Clinical data and endoscopic images were reviewed. To evaluate the precision of endoscopists’ diagnoses for this type of lesion, eight endoscopists with different experiences were recruited to judge the infiltration depth of these lesions and analyze the accuracy rate. Results We screened 520 patients and retrospectively identified 18 EGC patients with an invasive cancer-like morphology. The most common lesion site was the cardia (12/18, 66.67%). The coexisting submucosal lesions could be divided into solid (5/18, 27.78%) and cystic (13/18, 72.22%). The most common type of submucosal lesion was gastritis cystica profunda (12/18, 66.67%), whereas leiomyoma was the predominant submucosal solid lesion (3/18, 16.67%). Ten (55.56%) patients