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Purpose: We evaluated the relationship between the degree of osteopontin (OPN) expression in papillary thyroid carcinoma (PTC) specimens and the presence of the BRAF mutation and clinicopathologic variables. Methods: Fifty-six snap-frozen thyroid tumor samples, including those of 49 PTCs, four follicular adenomas, two follicular carcinomas, and one Hürthle cell adenoma, were studied. We performed reverse transcription-polymerase chain reaction (RT-PCR) to assess the OPN expression levels. We also tested the BRAF codon 599 mutations using RT-PCR with the direct sequencing method. All of the tumors were microscopically reexamined by a pathologist with a special interest in thyroid neoplasia. Results: OPN mRNA was significantly overexpressed in the PTC samples compared with other thyroid tumors (P = 0.011). In PTCs, the OPN expression level was higher in the BRAF mutation group than in the wild-type group (P = 0.041). Among the clinicopathologic variables, nonfollicular variant histologic subtypes (P = 0.002) and the presence of lymph node metastases (P = 0.042) were correlated with elevated level of OPN expression. Conclusion: OPN might play a crucial role in tumorigenesis and the progression of PTC.