Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) allow remarkable improvement of the overall survival (OS) of lung adenocarcinoma patients with sensitizing EGFR mutations. This retrospective study was aimed at determining whether spinal surgery improves the quality of life and OS of patients with spinal metastatic instability. Methods: We reviewed the data of 362 lung adenocarcinoma patients with EGFR sensitizing mutations which were administered EGFR-TKIs as first-line therapy. Eighty-six of these patients had spinal instability neoplastic scores (SINS) of >= 7 points; 45 of these patients subsequently required surgery (the surgery group), but the rest did not (the non-surgery group). The patients were evaluated for quality of life, pain severity, and spinal cord function at the time of diagnosis and after the failure of the EGFR-TKI treatment. Results: The OS of all the patients was 24.0 months, with 59.1% of the patients having bone metastases (spinal in 81.8%) at the time of the initial diagnosis. The OS was significantly lower in patients with bone metastasis than it was in those without it (19.0 months vs. 31.0 months, P<0.001) and in patients with SINS of >= 7 points than it was in patients with SINS of <7 (15.0 months vs. 21.0 months, P=0.038). Among patients with SINS of >= 7 those who underwent spinal surgery did not show any significant improvement in the OS as compared to those who did not undergo surgical treatment (17.0 vs. 10.0 months, P=0.119). At the time of EGFR-TKIs failure, pain and neurological function were significantly better among the patients who received surgical treatment than those who did not undergo surgery. The proportion of patients requiring secondary treatment in the surgery group was greater than the proportion requiring secondary treatment in the non-surgery group (88.8% vs. 68.2%, P=0.032). Conclusions: Bone metastasis, particularly if the SINS score is >= 7 points, is associated with poor survival in patients with EGFR-positive lung adenocarcinoma. We found that surgical treatment can be effectively used to prevent spinal cord dysfunction, provide pain relief for patients, and improve treatment acceptance and compliance.