Abstract Background. Thyroid nodules are the most common surgical disease of the thyroid. Fine‐needle aspiration biopsy (FNAB) is the most commonly employed tool for establishing a diagnosis. However, 15% to 25% of FNAB reports yield inconclusive results. Immunostaining of cytological smears from FNAB with galectin‐3 has been proposed as a tool for differentiating between benign and malignant nodules. We performed a systematic review to evaluate the utility of galectin‐3. Methods. Prospective studies of nodules with FNAB reports of “follicular neoplasm” and with a definitive diagnosis confirmed by histopathology were selected. Calculations of individual sensitivity, specificity, and positive and negative likelihood ratios were made. Results. The articles selected were those with the best methodological quality. Conclusion. Galectin‐3 could be a good tool to guide therapeutic decision in patients with thyroid nodules and FNAB results of follicular neoplasm, but available information has methodological flaws that precludes a definitive answer about galectin‐3 utility in the clinical setting. © 2007 Wiley Periodicals, Inc. Head Neck 2007