Abstract: Objective To explore the approach of clinical diagnosis and treatment strategy for patients with small pulmonary nodules (SPN)≤ 1.0 cm in size on CT. Methods We retrospectively analyzed the clinical records of 39 patients with SPN less than 1.0 cm in size who underwent lung resection at Nanjing Drum Tower Hospital from January 2005 to June 2011. There were 23 males and 16 females. Their age ranged from 31-74 (51.0±7.4) years. Nine patients had cough and sputum and other patients had no symptom. All the patients were found to have SPN less than 1.0(0.8±0.1)cm in size but not associated with hilum and mediastinal lymphadenectasis in chest CT and X-ray. The results of their sputum cytology and electronic bronchoscope were all negative. All the patients had no histologic evidence and underwent pulmonary function test prior to operation. Eleven patients had positron emission tomography/computer tomography (PET/CT)or single-photon emission computed tomography (SPECT)which was all negative. Thirteen patients underwent video-assisted minithoracotomy(VAMT) and 26 patients underwent video-assisted thoracoscopic surgery (VATS). Results The average operation time was 121.0±48.0 min. Patients after partial lung resection were discharged 4~5 d postoperatively, and patients after lobectomy were discharged 7 d postoperatively. All the patients had no postoperative complications. Twenty one patients were identified as lung malignancy by postoperative pathology, including 9 patients with adenocarcinoma, 7 patients with bronchioloalveolar carcinoma, 1 patient with small cell lung carcinoma, and 4 patients with pulmonary metastasis. Eighteen patients had benign lesions including 4 patients with sclerosing hemangioma, 4 patients with inflammatory pseudotumor, 2 patients with pneumonia, 3 patients with granuloma, 2 patients with tuberculosis, and 3 patients with pulmonary lymph node hyperplasia. The SPN were located in left upper lobe in 11 patients, left lower lobe in 6 patients, right upper lobe in 14 patients, right middle lobe in 1 patient, and right lower lobe in 7 patients. Conclusion The diagnosis of SPN ≤1.0 cm in size on CT should consider malignance in the first step to avoid treatment delay. Patients may have a 3-month observation period to receive selective antibiotic treatment, chest CT and X-ray review after 2 to 4 weeks. CT- guided hook-wire fixation is useful to help in precise lesion localization for surgical resection. VATS and VAMT are common and effective methods for the diagnosis and treatment for SPN.