Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increased frequency in modern clinical practice. Among other diagnostic modalities, fine-needle aspiration (FNA) biopsy of clinically suspicious thyroid nodules is becoming increasingly popular. Preliminary investigations have suggested that molecular diagnostic assays using tumor-specific markers may improve the sensitivity and accuracy of FNA and so may be expected to reduce the frequency of open surgical procedures by identifying those patients with demonstrably benign lesions who do not require definitive surgical excision of their lesions for diagnosis. At the same time, thyroid-specific mRNA assays (especially thyroglobulin mRNA testing) have been used by investigators in the postoperative follow-up of patients with thyroid cancer as a potential means of detecting tumor recurrence in the peripheral blood. Although these studies have not all reported unqualified successes--indeed, some problems based on both technical and biologic limitations have been identified-these assays still hold out the possibility that potentially important new advances in the management of patients with well-differentiated thyroid cancer may be offered by these and other molecular diagnostic methods.