Background: This paper aimed to evaluate the expression of REG gamma and characterize its clinical significance in papillary thyroid carcinoma (PTC). Material/Methods: In total, 54 patients with PTC who underwent partial or total thyroidectomy and cervical node dissection for PTC from February 2009 to September 2011 were retrospectively reviewed. Thyroid specimens and metastatic lymph nodes from 54 patients and normal thyroid tissues obtained from 13 volunteers were collected and analyzed. Tumor size, T-stage, and lymph nodes metastasis were recorded based on surgical pathology. Immunohistochemical (IHC) technology was performed to analyze REG gamma protein expression level. Corrections between the expression of REG gamma and the clinicopathological factors were analyzed. Results: All the normal thyroid tissues were REG gamma-negative. REG gamma was positive in 75.9% (41/54) of PTC tissues, of which 29 cases (29/42, 69.0%) were in T1-T2 stage and 12 cases (12/12,100%) were in T3-T4 stage. Positive REG gamma was found in 21 cases (21/24, 87.5%) in T1-T2 stage with lymph nodes metastasis, while 11 cases were in T3-T4 stage with metastases to lymph nodes (11/11, 100%). High level of REG gamma expression was significantly correlated with T-stage (P< 0.05) and lymph node metastases (P< 0.05). In addition, there was no statistically significant difference between the expression of REG gamma and age, sex, tumor size, or tumor multiplicity (P> 0.05). Using binary logistic regression model, positive REG gamma was identified as a significant independent predictor factor of lymph node metastasis in PTC. Conclusions: High expression of REG gamma seemed positively correlated with T-stage and lymph node metastasis in PTC tissues.