Diagnosis and treatment of solitary pulmonary nodule (SPN, less than 30 mm in diameter) has been a formidable problem in clinical work. It is often detected in medical examination or other disease examinations by chance. There are no corresponding signs and symptoms of SPN except those on the imaging, so it is difficult to make a correct diagnosis as early as possible. Literature shows that there is a certain probability of malignant SPN, so early correct diagnosis is the key factor in deciding the prognosis and appropriate treatment. With the accumulation of clinical experiences, the development of new fiberoptic bronchoscopy, highresolution CT, and videoassisted thoracoscopic surgery, as well as the evolution of some invasive examination technologies, it is less difficult in distinguishing benign from malignant SPN than ever before. In this article, we will make a comprehensive review on the development in the aspect of differential diagnosis of SPN.