Background: Non-small cell lung cancer (NSCLC) patients with extrathoracic metastasis (EM) are a highly heterogeneous cohort. Some of these patients could benefit from primary tumor surgery. This study aimed to identify potential NSCLC patients with EM suitable for primary tumor resection and to determine the optimal therapeutic strategy., Methods: NSCLC patients with EM were extracted from the Surveillance, Epidemiology and End Results database between 2010 and 2015. They were stratified into subgroups with single and multi-EMs. Cox regression analysis was adopted to identify prognostic factors for overall survival (OS). The Kaplan-Meier method was used to compare the OS among patients who received different treatment modalities., Results: The univariate Cox regression analysis demonstrated that advanced age, male sex, race (black), married status, squamous cell carcinoma, higher histological grade, advanced T or N stage, contralateral lung metastasis, multi-EMs, tumor size >2 cm, and lack of treatment were associated with poorer OS in patients with NSCLC (P<0.05). Multivariate Cox regression analysis revealed that the number of EM and treatment modalities were independent prognostic factors affecting OS (P<0.001). For patients with single EM, those who did not receive treatment and those who underwent single-agent chemotherapy, single-agent surgery, surgery combined with chemotherapy, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy had median OS times of 3.0, 11.0, 12.0, 26.0, 11.0, and 25.0 months, respectively. Compared to monotherapy, combination therapy showed significant benefits for patients with single EM in NSCLC. Furthermore, patients with single EM who underwent lobectomy, bilobectomy, or pneumonectomy had significantly longer survival than those who underwent sublobar resection, even when the primary tumor size was ≤2 cm (P=0.04)., Conclusions: Primary tumor surgery could benefit NSCLC patients with single EM; lobectomy was at least warranted to improve survival even for primary tumors with size ≤2 cm., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-516/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)