The distinction of thyroid carcinoma from benign thyroid neoplasm, as Well as the subtyping of papillary carcinoma (PC) and follicular carcinoma (PC), may he performed histopathologically in the majority of cases. However, in certain cases, it is difficult to histopathologically distinguish between PC and PC, as well as follicular adenoma (PA), PC and the dominant nodule of multinodular goiter (NING-DN). The present study aimed to determine the roles of the expression levels of the tight junction proteins claudin I, 4 and 7 in the differential diagnosis of PC:, PC, FA, MNG-DN, medullary carcinoma (MC) and anaplastic carcinoma (AC). The current study included 114 cases of histopathologically diagnosed thyroid neoplasia, which were distributed as follows: 29 FA, 18 MNG-DN, 47 PC, 10 PC, 5 MC and 5 AC. The expression levels of claudin 1, 4 and 7 were examined using immunohistochemical methods. The results revealed a significant difference in claudin 1 expression between malignant and benign thyroid neoplasms (P<0.001). Claudin 1 expression was not detected in any of the MNG-DN cases, and no significant difference in claudin 1 expression levels was identified between FA and PC (P=0.653). However, a statistically significant difference was observed between PC and PC: (P<0.001). Claudin 4 expression did not differ between malignant and benign thyroid neoplasms, neither between MNG-DN, PA and PC, nor between PC and PC (P=0.068, P=0.502 and P=0.481, respectively). Claudin 7 exhibited positive immunohistochemical staining in 107 patients (94%); however, no significant difference in claudin 7 expression levels was identified between malignant and benign thyroid neoplasms among MNG-DN, EN and PC (malignant, P=0.135; benign, P=0.470). Claudin 7 exhibited positive staining in all PC and PC cases. Theretbre, claudin 1 expression levels may he useful in distinguishing cases of PC and PC' with overlapping histopathological features, and provide a novel immunohistochemical marker for the subtyping of thyroid carcinoma.