Isolated small pulmonary nodules are single nodules or spherical lesions ≤3 cm in diameter, with sharp and clear margins, surrounded by normal lung tissue, and may be solitary or multiple, usually without pulmonary atelectasis, hilar lymph node enlargement, or pleural effusion. Isolated pulmonary nodules can be divided into two categories: malignant lesions and benign lesions. Malignant lesions mainly include primary lung cancer, carcinoid tumors and metastatic lung tumors, while benign diseases mainly include pulmonary malignant tumors, inflammatory pseudotumors, pulmonary tuberculosis spheres, pulmonary mycobacteria spheres, etc., which are mostly asymptomatic and unintentionally detected during physical examination, and may be accompanied by some common respiratory symptoms, such as blood in the sputum, cough, sputum and chest pain, but most of them are not specific. At present, it is generally believed that 50-60% of small isolated pulmonary nodules are benign lesions, but about half of them are malignant tumors. Therefore, it is important to define the nature of the isolated pulmonary nodule in order to develop a treatment strategy. Chest radiographs, CT and FDG-PET examinations are the main imaging methods used to evaluate small isolated nodules in the lung. Among them, chest radiography is used as a screening method to observe the size, margins, and calcification of nodules. CT has a higher sensitivity and specificity than chest radiographs, which not only clearly shows the morphology, size, and imaging characteristics of the surrounding tissues, but also allows dynamic comparison of the changes of small nodules through CT images at different times. Thin-section CT of the chest has higher resolution and should be the imaging method of choice to assess the nature of isolated small nodules in the lung. Among them, lobulation, burr and pleural depression sign are common CT imaging features of malignant tumors; while FDG-PET is a noninvasive imaging method that has been more widely used for malignant tumor diagnosis, staging and evaluation of treatment effect, which can show both the morphology of nodules and assess the metabolic status of nodules, and can be used as an option for preoperative routine screening of benign and malignant prediction and judgment of isolated pulmonary nodules. However, the use of FDG-PET alone for the diagnosis of small isolated pulmonary nodules is controversial because it is expensive, not easily accessible, and less sensitive for small nodules less than 10 mm in diameter. Pathologic diagnosis is the gold standard for confirming the nature of isolated pulmonary nodules. However, to obtain pathology, invasive tests must be performed. Fiberoptic bronchoscopy is the most common invasive test to obtain pathology of pulmonary lesions, but the rate of bronchoscopic detection is related to the size and location of pulmonary nodules. For peripheral pulmonary nodules less than 20 mm in diameter, the detection rate of bronchoscopy is extremely low. For this type of isolated pulmonary nodules, CT-guided needle aspiration biopsy may be a better diagnostic method with sensitivity and specificity of more than 90%, but the detection rate still depends mainly on the size of the nodule, the thickness of the puncture needle, the number of punctures, and the diagnostic ability of the cytologic pathology. In addition, considering the tissue heterogeneity of lung cancer cells, the sample size obtained from a puncture biopsy is small and sometimes does not allow for a definitive staging of lung cancer. The puncture may also lead to serious complications such as bleeding and pneumothorax. In recent years, a new type of electromagnetic navigation bronchoscope (ENB) has been used in clinical practice, which combines the advantages of spiral CT simulation bronchoscopy and traditional bendable bronchoscopy, and provides real-time guidance and positioning to accurately reach peripheral lung lesions that cannot be reached by conventional bronchoscopy and obtain specimens for pathological examination. Its complication rate is significantly lower than that of CT-guided needle aspiration biopsy. However, ENB is still a new technique that is not yet available, the evidence base is still insufficient, the indications are not clearly described in the relevant guidelines, and the expensive price and cost of the procedure is still a bottleneck. Surgery is the “ultimate method” for diagnosing the benignity of small isolated nodules in the lung, and can be performed concurrently with radical surgery for early stage non-small cell lung cancer. However, the choice of surgery as a diagnostic strategy must be balanced against the benefits of a definitive pathological diagnosis and further treatment and the risks of surgery. Both thoracoscopic and open-heart surgery are available for the diagnosis and treatment of small isolated lung nodules, and the choice of surgical approach depends on the patient’s specific situation. It is less invasive and does not cut off the chest muscles, resulting in relatively less postoperative pain and therefore faster recovery and less hospitalization time than conventional thoracotomy. Thoracoscopic surgery is used to determine the benignity and malignancy of small pulmonary nodules with a sensitivity and specificity of 100% and a mortality rate of only about 1%. For peripheral nodules diagnosed as non-small cell lung cancer, thoracoscopic lobectomy and mediastinal lymph node dissection are the standard radical surgical procedures. Thoracotomy is also the standard surgical approach for non-small cell lung cancer, but it has a relatively high complication rate and mortality. In addition, anatomic segmental lung resection or wedge resection is an acceptable treatment strategy for patients with small nodes or those who cannot tolerate lobectomy. With increasing health awareness, more and more small isolated pulmonary nodules are being detected. In this regard, we recommend that they need to be seen as soon as they are detected. In current clinical practice, the measures that can be taken after detection of a suspicious nodule are mainly CT, PET, CT-guided fine-needle aspiration biopsy, surgery, or observation and follow-up, or a combination of these five measures. However, each of the five methods has its own advantages and disadvantages, so how to give the most reasonable, safe and economical diagnostic strategy for lesions with different characteristics is the most important issue facing clinicians. With the progress and conclusion of various studies, we can give individualized diagnostic strategies based on relevant evidence-based medical evidence. It is believed that with the development of new technologies such as electromagnetic navigation bronchoscopy, the diagnosis of small isolated pulmonary nodules will become easier and safer.