Hürthle cells may be found in fine-needle aspirates of the thyroid (FNATs) from Hürthle cell tumors (HCTs) and nonneoplastic Hürthle cell lesions, including Hashimoto’s thyroiditis and goiter. To differentiate the characteristic cytomorphologic features from these lesions, the authors studied 38 surgically excised Hürthle cell lesions of the thyroid. Preoperative FNATs were reviewed for a number of architectural and cytologic features. The chi-squared and Fisher’s exact tests were used for statistical analysis. There were many statistically significant cytologic differences between HCTs and nonneoplastic Hürthle cell lesions. Statistically significant features indicating an HCT versus nonneoplastic Hürthle cell lesion included the following: a high percentage (> 90%) of Hürthle cells, single Hürthle cells (> 10%), cellular dyshesion, large nucleoli, significant nuclear pleomorphism, significant nuclear enlargement, absence of macrophages, absence of plasma cells, and absence of or few lymphocytes. The architecture of cell groups, cellularity, amount of colloid, and multinucleation appeared to be of no value. The presence of a high percentage of dyshesive Hürthle cells with large nucleoli, with some cells showing significant nuclear enlargement and pleomorphism, associated with a lack of lymphoplasmacytic inflammatory cells, appears statistically predictive of an HCT and should enable the differentiation of an HCT from a nonneoplastic Hürthle cell lesion.