The natural history of Hürthle cell (HC) lesions has been the focus of a considerable debate. The difficulties in defining the malignant potential of HC has led to the current designation of HC tumor, with the implication that it may behave as either a benign or a malignant lesion. The objective of our study was to verify the clinical and prognostic relevance of the cytological diagnosis of HC in the thyroid lesion, 10,950 consecutive patients (F/M = 5.6/1) with thyroid nodules were evaluated by means of fine needle aspiration biopsy (FNAB). Cytological diagnosis showed the presence of HC in 285 cases (2.6%), with a F/M ratio of 8.2/1. In 123 cases (43.2%) cytologic diagnosis resulted benign. A suspicious pattern of follicular neoplasm was observed in 159 cases (55.8%). Only in 3 cases (1%) thyroid carcinomas were preoperatively identified. No false positive or negative cases were observed. Among the HC lesions, 85 patients (29.8%) underwent thyroid surgery because of a malignant or suspicious cytologic diagnosis, continuous nodular growth despite LT4 therapy, mechanical compression or clinical judgement. The other two hundred patients were clinically evaluated and, one year later, repeated FNAB confirmed the cytologic diagnosis of benignity. Among the follicular neoplasm nodules, 80 cases (55.3%) were surgically explored, and thyroid carcinoma diagnosed in 30 of them (37.5%), this percentage being greater than that observed in the group of non-HC follicular neoplasm (17%). Pathologic criteria for malignancy (vascular invasion, transcapsular penetration, destructive capsular invasion) were described in 25 out of all carcinomas.