Thyroid cancer is the most common endocrine malignancy. Although the majority of thyroid cancers are well differentiated and have a favorable prognosis, a minor proportion are poorly differentiated malignancies, which show an aggressive behavior and are refractory to conventional cancer treatments. The molecular mechanisms underlying thyroid development and progression are incompletely understood. Most of thyroid tumorigenesis models propose that thyroid cancer originates from the normal thyrocytes that, via the accumulation of genetic alterations, acquire a malignant phenotype and the ability to metastatize. However, recent progress in clarifying the molecular mechanisms of thyroid embryogenesis/development and the discovery of fetal/stem-like cells within the thyroid gland, have raised the possibility that thyroid cancer originates from progenitor/stem cells. These cells have the ability to self-renew and to undergo multilineage differentiation, and are resistant to common anticancer treatments. Thyroid progenitor/stem cells have been isolated from thyroid cancer and the normal counterpart. Further insights in the biology of these cells will open new perspectives in terms of prevention, diagnosis and therapy of thyroid cancers, especially those with an aggressive behaviour. More effective protocols for the identification and isolation of thyroid cancer stem cells will allow us to specifically and safely target these cells with the aim to definitely eradicate aggressive thyroid cancers.