Thyroid nodules are a common clinical thyroid disorder. The prevalence of thyroid nodules in the general population in the United States is estimated to be 3% to 7% by palpation and up to 20% to 76% by ultrasonography. Thyroid nodules are more common in the elderly, in women, in iodine-deficient areas, and in people with a history of radiation exposure. There is no systematic epidemiological survey on thyroid nodules in China. The diagnosis and management of thyroid nodules is based on the identification of their benign and malignant nature in order to determine the subsequent treatment of the patient. Detailed history taking and physical examination are important in the evaluation of thyroid nodules. During the physical examination, attention should be paid to the location, size, texture, and mobility of the nodule, in addition to the presence of pressure pain in the neck and the presence of enlarged lymph nodes in the neck. The presence of certain factors predicts an increased risk of malignant nodules, including: history of radiation therapy to the head and neck, family history of medullary thyroid carcinoma (MTC), papillary thyroid carcinoma (PTC) and multiple endocrine adenomatosis type 2 (MEN2), age younger than 14 years or older than 70 years, male, hard, irregularly shaped, fixed and persistent nodules, hoarseness, dysphonia, and dysphagia, etc. A recent study suggests that patients with Hashimoto’s thyroiditis also have a somewhat increased risk of thyroid cancer. In a group of 613 patients with surgically treated thyroid nodules, the incidence of pathologically confirmed thyroid cancer was 45.7% and 29% in Hashimoto and non-Hashimoto patients, respectively (p=0.001). Most patients with thyroid nodules are asymptomatic and are found accidentally during physical examination or other neck examinations, but in some patients slowly progressive growing nodules (weeks or months) should be alerted to the possibility of malignancy, and cystic nodule bleeding should be noted if the nodule suddenly appears painful. Progressive enlargement and painful thyroid nodules should be considered as undifferentiated thyroid cancer and thyroid lymphoma. Comprehensive evaluation of thyroid nodules is a multifaceted process. The main tools used to evaluate thyroid nodules include high-resolution ultrasonography, thyroid function measurements and fine needle aspiration biopsy (FNAB) of thyroid nodules. Magnetic resonance imaging (MRI) and CT examinations are not very helpful in determining the benignity or malignancy of nodules. These examinations are mainly used to assess the relationship between the nodule and the surrounding tissues and to understand the presence or absence of airway compression and the extent of the thyroid gland behind the sternum. Laboratory tests The determination of thyroid function and autoantibodies are of great value in the evaluation of thyroid nodules. It has been reported in the literature that the prevalence of thyroid cancer correlates with serum thyrotropin (TSH) levels. High-functioning nodules with suppressed TSH are less likely to be malignant, and the prevalence of thyroid cancer increases to a certain extent as TSH levels increase (even within the normal range). Thyroid autoantibody tests are mainly used to diagnose Hashimoto’s thyroiditis. Recently, it has been reported in the literature that increased titers of thyroglobulin antibodies (TgAb) significantly increase the risk of thyroid cancer, but thyroid peroxidase antibody (TPOAb) levels have not been found to be associated with the risk of thyroid cancer. Calcitonin measurement is valuable for the diagnosis of MTC and is mainly used in patients with pre-surgical nodular goiter or a family history of MTC or MEN2. 2. Imaging imaging Thyroxine imaging is the only imaging method that can evaluate the functional status of nodules, but it is not necessary for the diagnosis of most thyroid nodules. In patients with low TSH levels or multinodular goiters, imaging can detect functional nodules or high-functioning adenomas. Functional thyroid nodules do not require further cytology in most cases, but it is important to note that there may be both functional and cold nodules (potentially malignant) in the same patient with an overall high-functioning multinodular goiter, which requires careful screening. To date, ultrasonography is the most sensitive test for evaluating thyroid nodules. This test not only helps to identify the nature of the nodule, but also allows for localization, puncture, treatment and follow-up of the thyroid nodule. Ultrasound is required for all patients suspected of having a thyroid nodule or who have an existing thyroid nodule. The ultrasound report should include the shape, size, and number of nodules, the state of the nodule margins, internal echogenic features, blood flow status, and the condition of the lymph nodes in the neck. Features of thyroid ultrasound that suggest malignant nodules include: hypoechoic nodules, microcalcifications, lack of peripheral halo, irregular nodule margins, and disturbance of blood flow within the nodule. The specificity of the above features is high, reaching more than 80%, but the sensitivity is low, ranging from 29% to 77.5%. One feature alone is not sufficient to diagnose malignant lesions. However, if two or more features are present at the same time or one of the features is present in hypoechoic nodules, the sensitivity of diagnosing malignant lesions can be increased to 87%-93%. In conclusion, ultrasonography is the most reliable and valuable diagnostic method for identifying benign and malignant nodules. 3. Fine needle aspiration biopsy of thyroid nodules FNAB should be performed in all cases where malignancy is suspected to distinguish the nature of the lesion (Figure 2) and to clarify the subsequent treatment. Indications for FNAB are solid hypoechoic nodules >10 mm in diameter; nodules of any size with suspected extraperitoneal growth or metastasis to lymph nodes in the neck; children or adolescents with a history of neck radiation exposure; first-degree relatives of patients with PTC or MTC; history of thyroid cancer surgery; and those with elevated serum calcitonin levels. For nodules <10 mm, FNAB should be performed if ultrasound reveals signs associated with malignant lesions; especially if 2 or more ultrasound suspicion criteria are present. For multinodular goiter, FNAB is usually performed on nodules with ultrasound signs of malignancy, but rarely on more than 2 nodules; FNAB is not necessary for "hot" nodules on isotope scan; if the lymph nodes in the neck are enlarged, FNAB must be performed on enlarged lymph nodes and suspicious nodules. For mixed (cystic solid) thyroid nodules, FNAB should be performed on the solid portion of the nodule, and the aspirated fluid specimen should be examined cytologically. The results of FNAB cytology are based on the results of the American College of Clinical Endocrinologists and the Italian Society of Clinical Endocrinologists. According to the 2010 joint guidelines of the American Academy of Clinical Endocrinologists, the Italian Society of Clinical Endocrinologists and the European Thyroid Society (AACE/AME/ETA), FNAB cytology findings are classified into five categories: category 1 is non-diagnostic, referring to inappropriate biopsies and insufficient numbers of follicular cells to make a determination; category 2 is benign lesions; category 3 is follicular damage, including follicular adenomas, Hü rthle cell damage and follicular variants of PTC; category 4 is suspected malignancy but does not meet adequate diagnostic criteria; category 5 is clearly malignant or positive lesions. Strategies to improve the diagnostic accuracy of FNAB include using ultrasound-guided FNAB; performing multi-point puncture sampling for suspicious nodules; considering re-FNAB and follow-up for benign nodules; for multinodular goiter, highly suspicious nodules can be selected for biopsy based on ultrasound findings; and at least 6 ultra-thin cell smears should be prepared for diagnosis after puncture. 4.Ultrasound-guided core needle biopsy Since FANB examination takes less material and the judgment of cytological findings often needs to be done by experienced physicians, there is still a significant portion of thyroid fine needle aspiration cytological examination in clinical practice that is difficult to determine its benignity and malignancy. For patients with thyroid nodules with inconclusive cytologic findings, ultrasound-guided core-needle biopsy (CNB) can be used when necessary to provide additional diagnostic information. Literature reports and our clinical practice confirm that CNB is a safe and well-tolerated test with high diagnostic accuracy and may be superior to FNAB as a complementary diagnostic tool for thyroid nodules because of the histological specimens taken. Clinical management: follow-up should be done For symptomatic nodules diagnosed as malignant and with tracheal and local compression, surgical excision is feasible, but regular ultrasound follow-up is sufficient for most asymptomatic benign nodules. Left thyroxine (L-T4) suppression therapy is not routinely indicated in these patients. L-T4 therapy does not result in shrinkage of most thyroid nodules and is used only in selected young patients in areas with combined hypothyroidism and iodine deficiency. Transdermal alcohol injection or radiofrequency ablation can be used to treat benign cystic thyroid nodules. Radioactive iodine treatment may also be used for some high-functioning nodules or toxic multinodular goiters diagnosed by nuclear imaging.