Considering these data, we focus on describing and discussing the putative relationship of OPN as a potential EMT regulator in the development of thyroid cancer, providing new clues regarding the molecular mechanisms by which OPN could modulate epithelial–mesenchymal plasticity in this tumor type, possibly generating evidence that can contribute towards the future development of new therapeutic, prognostic and/or diagnostic tools. This evidence concerns the gene SPP1 and thyroid cancer.