The routine use of thyroid FNAB caused profound changes in the management of thyroid nodules. FNAB allows a prompt identification and treatment of thyroid malignancies and avoids unnecessary surgery in patients with benign lesions, improving quality of life in patients with thyroid nodules. Furthermore, FNAB provides guidance for the type of surgery and reduces costs of care. On average, standard FNAB is nondiagnostic in 25% to 40% of cases, which include inadequate specimens and indeterminate (suspicious) diagnoses. In addition, a small percentage of false-negative diagnoses occur, which are unavoidable and raise concern of a late diagnosis of cancer. To minimize the limitations of FNAB, every center should reach and maintain a high standard of expertise in all of the steps of smear preparation and interpretation. Alternative modes of sampling or sample preparation may result in a reduction of nondiagnostic samples and better accuracy. Every center should set up clinical guidelines tailored to their own FNAB results and including the evaluation of clinical data. More work is needed to increase the accuracy of FNAB in suspicious cases. Toward this goal a variety of molecular markers have been evaluated; although none of them are ideal, some are promising. More studies need to be carried out in larger series to further evaluate the accuracy of these markers in identifying specific cancer histotypes within the group of suspicious lesions. It is hoped that, in the near future, the routine use of a combination of these markers will cost-effectively improve the diagnosis of malignant nodules classified as suspicious on traditional cytology. Statistical methods such as bayesian analysis or neural networks can be advantageously used to integrate different relevant information derived from family and personal history, clinical data, cytologic results, and evaluation of molecular markers.