Immunohistochemistry (IHC) is an economic and precise method to localize the presence of specific protein at cellular level in tissue. Although many papillary thyroid carcinomas do not require IHC to render a diagnosis, there are certain scenarios in which IHC are important. The major diagnostic applications of IHC include confirmation of papillary thyroid carcinoma in sites other than the thyroid, distinguish papillary thyroid carcinoma from other primary thyroid neoplasms in thyroid, and identify papillary thyroid carcinoma from secondary tumors to the thyroid. At research level, IHC could help identify prognostic information, identify underlying genetic alterations, and predict response to treatment in papillary thyroid carcinoma. The understanding of principle and recent advances in IHC will improve the diagnosis and management of patients with thyroid lesions including papillary thyroid carcinoma.