Objective To investigate the diagnostic method and surgical therapeutic outcome of small peripheral pulmonary nodules (diameter ≤2cm). Methods The data of 122 patients with small peripheral pulmonary nodules who were admitted from Jan. 2001 to Oct. 2010 and diagnosed by pathology postoperatively were retrospectively analyzed. The nodule diameter of nodules in 101 cases were 1-2 cm, and they were less than 1 cm in 21 cases. All the patients were examined by multislice spiral computed tomographic angiography (MSCTA), while 52 patients were examined by positron emission tomography/computed tomography (PET/CT), and 49 patients were subjected to CT-guided transthoracic needle biopsy (CTNB). The sensitivity, specificity and diagnostic accuracy were compared between the three methods for the diagnosis of lung cancer. Results Confirmed by postoperative pat hological examination, 29 patients were suffering from benign lesions (23.8%), and 93 were with malignant lesions (76.2%). In the 85 patients with non-small cell lung cancer, only 56 (65.9%) were in early stage (Ⅰa), and in 12(14.1%) hilar and mediastinal lymph node metastases were found. The sensitivity, specificity and diagnostic accuracy was 80.3%, 81.7% and 75.9% by MSCTA, 84.6%, 86.5% and 80.1% by PET/CT, and 91.8%, 88.6% and 100% by CTNB, respectively. The specificity of CTNB was better than that of MSCTA (P=0.045), and no significant difference was found in other indexes between MSCTA, PET/CT and CTNB (P>0.05). Conclusions MSCTA can serve as the first choice for the non-invasive diagnosis of small peripheral pulmonary nodules. Surgical operation is necessary for suspected malignant lesions, and CTNB can be selectively performed in patients who are considered to have benign lesions. In order to improve the speed and accuracy in locating the pulmonary nodules during the operation, the CT imaging should be carefully reviewed before operation in order to identify the location of the lesion, and CT-guided transthoracic needle biopsy could be done when necessary.