Differentiated thyroid cancers are the predominant malignancies of the thyroid. Due to advances in the understanding of the activation of the cell proliferation pathway at a molecular level, multiple genetic alterations have been linked to the development of thyroid carcinogenesis. Although the genetic alterations can be categorized into 7 categories, the BRAF mutation, RET/PTC, Pax8/PPARGamma, and dysfunctional Fas pathway have been most commonly described. Each of the gene alterations can ultimately result in cancer development, invasion and/or metastasis. This article provides a detailed review of the altered cell proliferation pathway activations found in thyroid carcinogenesis. The molecular targets that may be disrupted by therapeutic agents during the abnormal proliferation are also summarized.