BackgroundSurgery for thalamic lesions is generally challenging because they are deep-seated and surrounded by vital neurovascular structures. Whether neuronavigation via middle frontal gyrus endoport-assisted endoscopic resection for thalamic lesions is safe and effective remains to be further evaluated.Materials and MethodsTwelve patients treated surgically were retrospectively reviewed using the neuronavigation endoport-assisted endoscopy between January 2016 and April 2021 at Zhongshan Hospital of Fudan University. Preoperative and tumor-related variables, as well as postoperative outcomes, were also collected.ResultsAll lesions located in the medial part of the thalamus, and some of them expanded forward, downward, or backward. The median size of lesions was 29 mm (range 16-56 mm). The final pathology results showed 4 cases of benign lesions, 4 cases of low-grade glioma, and 4 cases of glioblastoma. All of the cases with benign lesions and low-grade glioma (100%) achieved GTR, while 3/4 (75%) of cases with glioblastoma achieved NTR, and 1 (25%) case obtained STR. None of the patients in this study have postoperative seizures. In the benign lesions and low-grade glioma group, worse Karnofsky performance status scores at discharge were 25%, and all achieved long-term postoperative survival. For patients with glioblastoma, 3/4 cases had worse Karnofsky performance status scores at discharge, and died within 6 months. ConclusionCombining the advantages of neuronavigation, endoscopy, and endoport techniques via the middle frontal gyrus approach can safely and effectively remove benign lesions and low-grade glioma in the medial part of the thalamus.