Background and Aims Endoscopic thyroid cancer surgery via breast approach has been widely carried out. However, whether a thorough lymph node dissection, especially the dissection of the lower neck level Ⅵ and Ⅳ lymph nodes, can be completed under the endoscope in patients with lateral neck lymph node metastasis remains controversial. This study was conducted to summarize and analyze the clinical data of patients undergoing endoscopic thyroidectomy plus lateral cervical lymph node dissection via breast approach combined with transoral approach performed by the author's team to investigate the necessity and safety of adopting this procedure.Methods The data of 63 patients with papillary thyroid cancer undergoing endoscopic thyroidectomy plus central and lateral neck dissection in Zhongshan Hospital of Xiamen University from February 2015 to December 2021 were reviewed. Of the patients, 41 cases underwent endoscopic central and lateral neck dissection via breast approach combined with transoral approach (combined approach group), including 12 cases undergoing complementary level VI and IV lymph node dissection via transoral approach after thyroidectomy plus central and lateral neck dissection via breast approach, and the other 29 cases undergoing appropriate integration of surgical procedures via both breast and transoral approaches, without additional complementary level Ⅵ and Ⅳ lymph node dissection; 22 cases underwent endoscopic thyroidectomy and lateral neck dissection via breast approach alone (breast approach group). The main clinical variables were compared between the two groups of patients.Results There were no differences in age, sex, and tumor size between the two groups of patients (all P>0.05). Lymph nodes were detected in the specimens of 8 cases among the 12 patients undergoing complementary lymph node dissection in the combined approach group. Positive lymph nodes were found in 2 of them. In combined approach group and breast approach group, the total numbers of central compartment lymph nodes obtained were 8.80±5.78 and 8.23±3.53, and the total numbers of lateral cervical lymph nodes retrieved were 31.49±14.90 and 29.05±7.80, respectively. Both differences had no statistical significance (both P>0.05). There were no significant differences between the two groups in the operative time, the length of postoperative hospital stay, and the incidence rates of complications such as postoperative bleeding, recurrent laryngeal nerve paralysis, hypoparathyroidism, accessory nerve injury, chyle leak and Horner's syndrome (all P>0.05). During postoperative follow-up, recurrence of postoperative lateral lymph node metastasis occurred in one patient in combined approach group, and recurrence of lymph node metastasis of the dissected side was found in one patient in breast approach group.Conclusion Endoscopic thyroidectomy plus lateral cervical lymph node dissection via breast approach combined with transoral approach is safe and effective. It has a similar efficacy as that via breast approach alone. Still, the positive lymph nodes detected by complementary lymph node dissection suggest that endoscopic lateral cervical lymph node dissection via breast approach combined with transoral approach may have particular application value for those with more lymph node metastasis. However, the number of cases is small, and the follow-up time is relatively short in this study, so this method's safety, effectiveness, and necessity should be further evaluated by multi-center, large-sample controlled studies and long-term follow-up results.