OBJECTIVE Fine-needle aspiration biopsy (FNAB) is a technique in which a fine needle is introduced into a mass, cellular material is aspirated, and a cytological diagnosis is rendered. It separates reactive and inflammatory processes that do not require surgical intervention from neoplasia and benign from malignant tumors. FNAB lends itself to the diagnosis of palpable head and neck masses, in particular, those that persist following antibiotic treatment. METHODS This clinical state-of-the-art review article is intended to provide an overview of the clinical use of FNAB in the management of head and neck masses. Relevant case histories are used to illustrate this point. RESULTS Fine-needle aspiration biopsy has a high overall diagnostic accuracy of 95% for all head and neck masses, 95% for benign lesions, and 87% for malignant ones. CONCLUSIONS There are virtually no contraindications, and complications are minimal. Advantages of FNAB are that it is safe and simple, it can be performed as an outpatient procedure, and it is well tolerated by patients. In the present managed care environment, it also proves cost-effective. The diagnosis is readily known to the clinician, and appropriate treatment modalities can be discussed with the patient. It is recommended as a first line of investigation in palpable head and neck masses.