The authors discuss the principal aspects concerning the preoperative characterization of thyroid nodules, in particular those with follicular histology, and illustrate the potential clinical impact of a new diagnostic test-method, named "galectin-3 thyrotest", which is based on the immunodetection of galectin-3 molecule in cytological specimens derived from thyroid nodular lesions. This diagnostic test method, which consistently improves the accuracy of conventional cytology, has been recently validated in a large international multicenter study and is going to impact hardly the clinical management of patients bearing thyroid nodular diseases. The rationale of this new diagnostic approach, the possibility to improve its performance in selected cases by using large needle aspiration biopsy (LNAB) together with technical and operative details are presented and discussed.