AbstractThe efficacy of thyroid (FNAB) processed by liquid‐based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto‐histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied.150 cases of HT processed by conventional smear (CS) in 1996–98 and 670 with LBC in 2005–2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow‐up (including a second FNA or surgery) was done in 92 cases, in the second period in 116.In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005–2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME‐1 and Galectin‐3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC.LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc.