The use of molecular assays to analyze clinical tissues in the diagnosis and management of thyroid cancer, similar to other tumors, will likely allow for more accurate characterization of the aggressiveness of individual tumors and may allow for the early diagnosis of recurrence. The application of these methods to thyroid nodules and nodal metastases is less encumbered by difficulties arising from amplification of transcripts in non-thyroid cells. For these tissues, these assays are likely to be used clinically in the near-future. New data arising from cDNA arrays identifying novel markers of malignancy or tumor aggressiveness make this a growing area of interest. The use of molecular assays in diagnosing distant metastases is more problematic due to issues with ectopic expression of either full length or splice variants of genes thought to be thyroid-specific. Assay quantitation is a complex problem owing to variability in the level of expression of "housekeeping" genes and the variety of phlebotomy and RT-PCR methods reported. Additional research in this area is clearly required before a recommendation can be given regarding clinically applicability of these tests.