Design: Fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic tool in the diagnosis of thyroid nodules. A cytologic diagnosis of follicular neoplasm with atypical cells of undetermined significance (FN/AUS) implies that the selection of patients between surgery and follow-up is difficult. In this setting immunocytochemical stainings might be helpful. The efficacy of a panel made up of HBME-1 and Galectin-3 antibodies is evaluated in cases processed by liquid-based cytology (LBC). Methods: Out of 7091 thyroid FNAB processed by LBC method, 120 cases undergoing surgery successively were selected. These cases were classified as benign lesion (BL, eight cases), FN, including the ACUS category of the Bethesda classification (FN/AUS, 50 cases), suspicious for malignancy (SM, 59 cases), and malignant neoplasm (MN, three cases). Immunostains for HBME-1 and Galectin-3 were carried out on the LBC slides. Results: All MN and BL were histologically confirmed. FN/AUS and SM showed a malignancy risk of 24 and 72.9% respectively. The complete immunocytochemical panel was positive in 83.3% of the cases resulting in malignancy and negative in 87.5% of cases resulting in benign histology. Among the FN/AUS, the complete positive immunocytochemical panel was detected in 76.9% of cases resulting as malignant and the complete negative immunocytochemical panel was observed in 96.8% of cases resulting as benign at histology. Conclusions: The expression of HBME-1 and Galectin-3 in cases classified as FN/AUS on LBC-processed FNABs can effectively distinguish lesions, which need immediate surgery (high risk or FNH or Thy 3h) from those which can be followed-up (low risk or FNL or Thy 3l).