The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, its noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism.