Acromegaly results from oversecretion of growth hormone and subsequent insulin growth factor-I. Some studies have described an association between acromegaly and increased risk of some cancers, including thyroid cancer, the most common endocrine malignancy. It is well known that follicular thyroid cells express IGF-I receptor and that GH and IGF-I have both proliferative and anti-apoptotic effects and their hypersecretion may theoretically induce tumor development and stimulate its growth, despite the fact that research data is conflicting and population-based data on thyroid cancer and acromegaly is rare. Some molecular alterations, including point mutations in BRAF and RAS genes and RET/PTC gene rearrangements, have been associated with oncogenesis of PTC. However, the implications of these genetic markers in the development of PTC in patients with acromegaly are not yet well known. In this chapter, we discuss epidemiology, pathogenesis, molecular biology aspects, and how to screen and to manage acromegalic patients with nodular thyroid disease and thyroid cancer.Keywords: acromegaly and thyroid cancer, IGF-I and cancer, thyroid and acromegaly, GH and cancer, molecular markers and thyroid cancer Knowledges on Thyroid Cancer 2 2. Epidemiology