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Objective: Thyroglobulin measurement is the cornerstone of modern management of differentiated thyroid cancer, with clinical decisions on treatment and follow-up based on the results of such measurements. However, numerous factors need to be considered regarding measurement with and interpretation of thyroglobulin assay results. Design: The present document provides an integrated update to the 2013 and 2014 separate clinical position papers of our group on these issues. Methods: Issues concerning analytical and clinical aspects of highly-sensitive thyroglobulin measurement will be reviewed and discussed based on an extensive analysis of the available literature. Results: Thyroglobulin measurement remains a highly complex process with many pitfalls and major sources of interference, especially antithyroglobulin antibodies, need to be assessed, considered and, when necessary, dealt with appropriately. Conclusions: Our expert consensus group formulated 53 practical, graded recommendations for guidance on highly-sensitive thyroglobulin and TgAb in laboratory and clinical practice, especially valuable where current guidelines do not offer sufficient guidance. [ABSTRACT FROM AUTHOR]