Papillary carcinoma of the thyroid is mainly diagnosed with histopathologic features. Classical papillary architectures are important but nuclear change is the essential diagnostic element. Papillary architecture may be seen in benign lesions such as in hyperplastic areas of the follicular neoplasms, multinodular goiter and Grave's disease. Differential diagnosis of papillary carcinoma and papillary hyperplasia is very important for clinical management. Some authors have reported that Epithelial Membrane Antigen (EMA) and S-100 protein expression would be valuable and helpful in identifying papillary neoplasia and distinguishing it from papillary hyperplasia. In this study, EMA and S-100 protein expression of 14 papillary thyroid carcinomas and 13 papillary hyperplasias were studied by using immunohistochemical methods. In 14 papillary carcinomas, 9 showed diffuse and 3 revealed focal S-100 protein nuclear and cytoplasmic immunostaining. Two cases were not stained. All of the 13 papillary hyperplasias were negative for S-100 protein. EMA expression was observed in the apical cytoplasmic location of 11 papillary carcinomas except one case that showed diffuse cytoplasmic staining and one which was negative. In the papillary hyperplasias, 7 revealed both cytoplasmic and apical cytoplasmic staining. One case showed only cytoplasmic staining. Five cases were negative for EMA. The difference in the S-100 protein expression is significant, however immunostaining of EMA is similar in both lesions. We concluded that differential diagnosis of papillary structures in carcinomas and hyperplasias was mainly diagnosed on the histopathologic features but S-100 protein expression could be helpful in difficult cases.