Objective: To assess usefulness of cytokeratin 19 (CK19), thyroperoxidase (TPO), Hector Battifora mesothelial epitope-1 (HBME-1) and galectin-3 (GAL3) in evaluation of aggressive behavior of PTCs. Methods: All available clinical and pathological data were reviewed in 168 papillary thyroid cancer patients; while the values as predictive markers of PTC were tested by univariate and multivariate analysis. Results: According to the univariate set of tests, positive expression of CK19 and negative expression of TPO correlated significantly with total tumor diameter (P < 0.05); But there was no association of positive CK19 expression and negative expression of TPO with gender, age, capsular invasion or lymph node metastasis. Moreover, there was no association of positive HBME-1 and galectin-3 expression with clinical aggressive behavior of PTCs. Conclusion: High expression of CK19 and negative expression of TPO indicate total tumor diameter of PTC, but expression of CK19, TPO, HBME-1 and GAL3 has no values in the identification of PTCs with other potentially aggressive behavior.