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Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We have found that bone morphogenetic proteins (BMP), especially BMP-2, may play an important role in ectopic chondrogenesis in this tumor. Bone morphogenetic protein-6 was reported to be related to the osteogenic metastasis of prostatic carcinomas. The relationship between BMP-6 expression and chondroid tissue formation is investigated. Twenty-three pleomorphic adenomas were examined immunohistochemically. The overexpression of BMP-6 was observed in 10 pleomorphic adenomas of the major salivary glands (43.5%), and no evidence of BMP-6 expression in any of the nine pleomorphic adenomas of the palate. Bone morphogenetic protein-6 was immunolocalized in the lacuna cells of the chondroid tissue, in which type II collagen was localized. Bone morphogenetic protein-6 was expressed in inner ductal cells of the tubulo-glandular structures in the pleomorphic adenomas. This finding indicates that BMP-6 may be associated with the differentiation of inner ductal cells. Bone morphogenetic protein-6 was expressed weakly in neoplastic myoepithelial cells in the myxoid areas, which may be related to the production of extracellular matrices. Bone morphogenetic protein-6 has a role in chondroid formation, and also tubulo-glandular differentiation in pleomorphic adenomas. In conclusion, a large portion of pleomorphic adenomas of the salivary gland origin, but not of palate origin, was shown to overexpress BMP-6 protein.