To investigate the efficacy and safety of endoscopic multi-band mucosectomy (EMBM) for the treatment of early esophageal cancer and mucosal intraepithelial neoplasia, and the relationship between morphology and pathological histological staging. Methods Forty-two cases of EMBM for esophageal mucosal lesions were collected from August 2007 to October 2011 in our department, including 21 males and 21 females with a mean age of 56.5 years (33-82 years), all of whom were single lesions. After routine endoscopic examination, the lesions were detected by NBI to show the extent of the lesions, and ultrasound endoscopy was performed for biopsy suggestive of cancer in order to clarify the depth of lesion infiltration. The lesions were resected by EMBM with intravenous anesthesia for those without contraindications, and heart rate and oxygen saturation were closely monitored during the operation. In this group, all 42 lesions were completely resected in one operation, using 1-11 skin rings respectively, and 85.7% (36/42) of the cases were operated under intravenous anesthesia. 3 cases had significant intraoperative bleeding, which were successfully stopped under endoscopy, and 1 case had esophageal perforation, which was successfully treated conservatively by clamping the wound with a titanium clip. The pathological diagnosis was high-grade intraepithelial neoplasia in 15 cases (including 2 cases of esophageal intramucosal carcinoma); low-grade intraepithelial neoplasia in 5 cases; polyp/squamous epithelial inflammatory hyperplasia in 10 cases; smooth muscle tumor in 7 cases; and others in 3 cases. The median follow-up time was 10 months (1-33), and there was no recurrence in all cases during the follow-up period. Conclusion EMBM can be one of the effective methods for treating early esophageal cancer or precancerous lesions. The operation of this method is relatively simple, and strict mastery of indications and operation specifications can reduce the occurrence of complications. In a typical case, Mr. Ning, 82 years old, was admitted to the hospital for endoscopic treatment of esophageal lesions found by gastroscopy due to epigastric fullness and discomfort (Figure 1). A flat elevated lesion with a central longitudinal depression indicating roughness and unevenness was seen in 33-35 cm of the esophagus; ② NBI imaging; ③ marking the extent of the lesion; ④, EMBM sleeve cut lesion; ⑤ post-excisional trauma; ⑥ pathology showed (HE staining, 200×) intramucosal carcinoma. Case 2, Mr. Qiu, 67 years old, was admitted to the hospital for more than 2 months due to retrosternal discomfort. In June 2011, he underwent external electronic gastroscopy: esophageal 25cm-31cm mucosal roughness with superficial erosion, Lugol’s fluid staining without staining, pathology: esophageal mucosa squamous epithelium high-level intraepithelial neoplasia (intra-mucosal carcinoma), EMBM was performed on June 30, 2011, and no recurrence was seen in 6 months of endoscopic follow-up. (Figure 2) ① esophageal 25cm-31cm mucosal roughness with superficial erosion; ② scope of marking; ③ EMBM sleeve cut lesion; ④ trauma; ⑤ pathology: high grade intraepithelial neoplasia; ⑥ 3 months postoperative review: scar formation, no recurrence and residual