Human transferrin receptor 1 (TfR1/CD71) is expressed on malignant cells at levels several fold higher than those on normal cells and its expression can be correlated with tumor stage or cancer progression. In previous studies, we found an aberrant expression of this receptor in thyroid carcinomas (Magro G et al., 2011). Herein, we assessed the expression and the localization of TfR1 in human cell lines of follicular and anaplastic thyroid tumor by Confocal Laser Scanning Microscopy on single cell and Western Blot analysis on total cellular lysate. The changes in cell growth and the activation of Erk1/Erk2 pathway were also evaluated. Our results showed that TfR1 appeared expressed at high levels in both thyroid cancer cell lines, even if it was more evident in the anaplastic ones. TfR1 was prevalently localized in the cytosol and in the mitochondria in the thyroid follicular cell lines, whether in the anaplastic cancer cell lines it was also localized into the nuclear compartments. In parallel, an activation of Erk1/Erk2 pathway in the both cell lines was observed. Our findings indicate that TfR1 plays a fundamental role in thyroid cancer progression promoting cell signaling probably thought Erk1/Erk 2 pathway, and also suggest that it might represent an important target for thyroid cancer therapy.