Thyroid nodules are epidemic with the rising use of high-resolution thyroid ultrasonography for health screening. The primary aim in investigating a thyroid nodule is to exclude the possibility of malignancy, which occurs in about 5% of nodules. Initial history taking and physical examination should focus on the clinical risk factors associated with thyroid cancer. Measurement of thyroid stimulating hormone (TSH) is the only biochemical test routinely needed to exclude autonomously functioning nodules. Thyroid ultrasonography-guided fine needle aspiration biopsy (US-FNA) is the most accurate standard diagnostic test for most thyroid nodules. Ultrasonographic features of nodules associated with increased risk of thyroid cancers include hypoechogenicity, microcalcification, irregular spiculated margin, taller-than-wide, Doppler signal in the nodules, and suspicious cervical lymphadenopathies. These findings are helpful in risk stratification of the nodules and in deciding which nodule should be sampled in multinodular goiters. The success of the procedure heavily depends on the experience and expertise of the clinicians. Knowledge on basic US-FNA techniques and some tricks is very important to improve overall diagnostic yields. Practically critical issues related to US-FNA are emphasized based on several guidelines and author's experiences.