Two recent studies showed that high TSH levels, even within the reference range, are associated with increased risk of development of papillary thyroid cancer in patients with thyroid nodules. The paper by Fiore and coworkers from the University of Pisa in this issue of ERC confirms this in a very large cohort of subjects (more than 10,000), and extends the observation by showing that the converse is also true. Thus, patients with low TSH levels, such as those with thyroid autonomy, have diminished risk of thyroid cancer. These findings suggest that TSH may play a fundamental role in thyroid cancer initiation or progression. Fiore, E et al. Endocrine-Related Cancer, 2009. In press. DOI:10.1677/ERC-09-0036