Thyroid nodules are one of the most prevalent and difficult to manage endocrine diseases, mainly because there is no specific method to distinguish benign from malignant nodules so far. Some symptoms or signs are of reference value in the diagnosis of thyroid cancer, such as painless enlargement of lymph nodes in the neck, hoarseness, hard texture of nodules, enlargement or hardening of nodules in a short period of time, and sensation of foreign body or obstruction in swallowing. Younger patients with solid, hard thyroid nodules, nodules with calcification or painless enlargement of lymph nodes in the neck are more likely to be malignant. Unlike most malignant tumors, thyroid cancer is not most prevalent in the elderly, but more likely to invade young and middle-aged people, which may be related to the involvement of sex hormones in the development of thyroid cancer…. Key points of clinical evaluation for differentiation of benign and malignant thyroid nodules:Family history of thyroid cancer, history of irradiation to the neck, age <15 years, male, rapid growth of nodules, persistent hoarseness and dysphonia after excluding vocal cord lesions (such as inflammatory reaction or polyps), irregular shape of nodules, adhesion and fixation to surrounding tissues and other clinical features often suggest that the nodules may be malignant. High-resolution ultrasonography is the preferred method for evaluating thyroid nodules, but its diagnostic ability is related to the clinical experience of the sonographer. The following ultrasound signs help to differentiate benign from malignant thyroid nodules and suggest a high probability of thyroid cancer: solid hypoechoic nodules; nodules with an abundant blood supply (in the presence of normal TSH); nodules with irregular morphology and margins, halo absence; microcalcifications, pinpoint diffuse distribution or clusters of calcified foci; accompanied by abnormal ultrasound images of cervical lymph nodes (e.g., round lymph nodes with irregular or blurred borders, The lymph nodes were found to be round, with irregular or blurred borders, uneven internal echogenicity, internal calcification, poorly demarcated skin and medulla, and loss of lymphatic portals or cystic changes). If multiple signs are present, the specificity of the nodule for malignancy is high. CT and MRI are important in determining the presence of lung, bone and brain metastases. Currently the best method to distinguish benign or malignant thyroid nodules is ultrasound-guided fine-needle aspiration cytology (FNA) of thyroid nodules. Fine needle aspiration biopsy (FNAB) can be considered for all thyroid nodules >1 cm in diameter. Fine needle aspiration of thyroid nodules is performed with a very fine needle, and thyroid tissue is aspirated for cytology during puncture. It is the gold standard for differentiating benign from malignant thyroid nodules and is an effective method for the diagnosis and differential diagnosis of many thyroid diseases. The tissue aspirated by fine needle aspiration is hidden in the needle core due to negative suction, so it will not leak out and contaminate other levels of tissue, and there is no risk of tumor spread. To obtain sufficient specimens, 3 to 6 aspirations are required. For cystic thyroid nodules, it is advisable to aspirate the marginal parenchymal parts of the nodule with a fine needle under the guidance of ultrasound, rather than aspirating the cystic fluid or debris. The diagnostic accuracy of FNA for lymph node metastases is up to 100%, but the sensitivity of FNA for primary thyroid foci is not satisfactory, only 55.88%. The sensitivity, specificity, and accuracy of FNAC are influenced by various factors such as puncture technique, sampling site, staining method, and cytopathological diagnostic experience. All patients with thyroid nodules should have serum TSH and thyroid hormone levels measured. When nodules are associated with decreased serum TSH, thyroid iodine-131 or technetium-99m nuclide imaging can determine whether the nodule has autonomic uptake (“hot nodules”). The vast majority of “hot nodules” are benign lesions such as autonomic thyroid function adenomas, which generally do not require fine needle aspiration biopsy (FNAB). Surgery is preferred for the management of malignant thyroid nodules. For benign lesions, the majority of patients do not require treatment, and follow-up is the mainstay, requiring review every 6 to 12 months, with thyroid ultrasonography and repeat thyroid FNAC if necessary. If it grows slowly or becomes smaller, benign lesions are likely, while if it grows rapidly, it suggests a high possibility of malignancy. Surgical removal of purely benign nodules is not effective and is highly prone to recurrence. Suspected malignant and undiagnosed thyroid nodules should have a repeat FNAC, which will result in a clear diagnosis in 30% to 50% of patients. If the diagnosis is not confirmed by repeated FNAC, especially if the nodule is large and shows local pressure symptoms, surgical removal can be performed.