Abstract: Objective To study the expression and significance of CK19, Galectin-3 and TPO in the differential diagnosis between benign and malignant papillary thyroid hyperplasia.Methods The expression of CK19, galectin-3 and TPO in 53 cases of papillary thyroid lesions, including 32 with papillary thyroid carcinoma and 21 with papillary thyroid hyperplasia, were detected by immunohistochemical SP method.Results The positive rates of CK19 and galectin-3 in the papillary thyroid carcinoma were 97% and 94% respectively, and those were 19% and 14%respectively in the papillary thyroid hyperplasia.There was significant different between papillary thyroid carcinoma and papillary thyroid hyperplasia in CK19 and galectin-3 expression(P＜0.05).The positive rates of TPO in the papillary thyroid carcinoma and papillary thyroid hyperplasia were 6% and 95% respectively(P＜0.05).Conclusion CK19, galectin-3 and TPO are useful markers for the differential diagnosis between benign and malignant papillary thyroid hyperplasia.It is better for CK19 using together with galectin-3 and TPO.