e21151 Background: The distinction between malignant and benign lesions of the thyroid gland often requires histological demonstration, once the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers have been studied by immunocyto- and immunohistochemistry techniques, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions. Methods: A systematic review of MEDLINE’s published articles was performed. After establishing the inclusion and exclusion criteria, 65 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed, and global values of sensitivity, specificity, area under the ROC curve (AUC), and diagnostic odds ratio (dOR) were calculated. Results: The positivity ofCK-19 for the diagnosis of malignant thyroid lesions demonstrated sensitivity of 81% (IC95%: 79-83%), specificity of 73% (IC95%: 70-75%), AUC of 87,5% and dOR of 14,7 (IC95%: 8,2-26,4); for Gal-3, sensitivity of 82% (IC95%: 81-84%), specificity of 81% (IC95%: 79-82%), AUC of 90% and dOR of 23,4 (IC95%: 14,0-39,1); and for HBME-1, sensitivity of 77% (IC95%: 76-79%), specificity of 83% (IC95%: 82-85%), AUC of 92,8% and dOR of 41,0 (IC95%: 21,4-78,4). The association of the three markers determined sensitivity of 85% (IC95%: 78-90%), specificity of 97% (IC95%: 90-99%), AUC of 93,3% and dOR of 95,1 (IC95%: 25,2-359,1). Conclusions: The search for new molecular markers must continue in order to enhance the diagnostic accuracy of the differentiation between malignant and benign lesions of the thyroid gland, since the results found still show persistency of false-negative and false-positive tests.