To determine the role of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the evaluation of incidentally diagnosed nonpalpable thyroid nodules (NP-TN), we compared the diagnostic yield of US-FNAB in NP-TN larger than 10 mm in diameter, with palpation-guided (P-FNAB) in palpable thyroid nodules (P-TN) in the same hospital setting. Of 108 consecutive patients with NP-TN (female/male: 97/11, age: 55.2 +/- 14.3, mean +/- SD), malignancy was identified in 8 patients (7 with thyroid papillary carcinoma, 4 of which had extrathyroidal spread, and 1 patient had metastasis of pulmonary adenocarcinoma). Male gender was associated with higher prevalence of malignancy (p = 0.09) while calcification and/or cystic degeneration of the nodule did not predict the cytological findings. Malignancy was identified in 16 of 151 consecutive patients with P-TN (female/male: 139/12, age: 44.1 +/- 9.5, mean +/- SD) indicating a similar rate of malignancy in both NP-TN and P-TN. In the P-TN group thyroid cancer was more common in males (p = 0.007), and the US properties of the nodule did not predict its cytological diagnosis. In conclusion, because similar rates of cancer are detected by FNAB in both NP-TN and P-TN, an FNAB is recommended for NP-TN larger than 10 mm.