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This paper provides an overview on the biology, monitoring and management of differentiated thyroid cancer (DTC), with particular attention to issues of relevance to clinical chemistry. The incidence of DTC appears to be increasing and management strategies are evolving as we learn more about its natural history and response to therapy. Clinical chemistry techniques play a central role in these protocols. Technical limitations inherent in current monitoring tools can hamper follow-up, although progress is being made. The molecular basis of DTC is being delineated with the potential to develop new strategies for diagnosis, monitoring and management of this condition.