Objective To analyze the expressions of galectin-3， human bone marrow endothelial cell-1 （HBME-1），cytokeratin （CK）19， and RET in benign and malignant thyroid tumor and to discuss their clinical significances. Methods The clinicopathologic and immunohistochemical staining data of 131 patients with benign and malignant thyroid tumor were analyzed retrospectively， including 45 patients with malignant thyroid tumor， 86 patients with benign thyroidtumor. The expressions of galectin-3， HBME-1， CK19， and RET in the benign and malignant thyroid tumor were detectedby immunohistochemical staining. Results The positive expression rates of the galectin-3， HBME-1， CK19， and RET in the malignant thyroid tumor were 97.8% （44/45）， 88.9% （40/45）， 100% （45/45）， and 71.1% （32/45）， respectively，which in the benign thyroid tumor were 9.3% （8/86）， 12.8% （11/86）， 37.2% （32/86）， and 8.1% （7/86）， respectively， the differences were statistically significant （P＜0.05）. The diagnostic sensitivity， specificity， and accordance rates were 97.8 %， 90.7%， and 93.1% for the galectin-3， respectively；88.9%， 87.2%， and 87.8% for the HBME-1， respec-tively；100%， 62.8%， and 75.6% for the CK19， respectively；71.1%， 91.9%， and 84.7% for the RET， respectively. Conclusions The expression levels of galectin-3， HBME-1， CK19， and RET in malignant thyroid tumor are significantly higher than those in benign thyroid tumor. Galectin-3， HBME-1， CK19， and RET can be important factors for identifying the benign and malignant tumor and their biological behaviors. Galectin-3 has a high reference value in the diagnosis of thyroid carcinoma.