Thyroid carcinoma derived from the thyroid hormone-producing follicular epithelium is the most common thyroid malignancy. While the morphologic diagnosis of conventional papillary thyroid carcinoma is simple, thyroid tumors with a follicular pattern are sometimes a diagnostic challenge. It is in the latter group of thyroid neoplasms that ancillary diagnostic tests such as immunohistochemistry may be of great help. Furthermore, while most differentiated thyroid carcinomas have an excellent prognosis, a subset of these tumors may progress to a poorly or undifferentiated phenotype indicating an aggressive biologic behavior that may lead to systemic spread and death. Application of immunohistochemistry to identify a subset of thyroid carcinoma that may progress to a biologically aggressive phenotype may help in the management of patients with thyroid carcinoma. This review discusses the role of immunohistochemistry in the diagnosis and progression of thyroid carcinoma is discussed.