Parathyroid hormone-related peptide is one of the most important regulators of chondrocyte proliferation. Although cartilaginous neoplasms express different collagens, including Types II and X, the pathogenesis of these tumors has not been elucidated. The current study examined the hypothesis that parathyroid hormone-related peptide is expressed in cartilaginous neoplasms and its level of expression may correlate with the proliferative rate of cartilaginous neoplasms with higher levels in more malignant tumors and lower levels in benign lesions. Two hundred thirty-four biopsy and resection specimens of benign and malignant cartilage tumors from 179 patients were retrieved from surgical pathology archival material and analyzed immunohistochemically using an antibody to human parathyroid hormone-related peptide. Most cartilaginous neoplasms had some level of expression of parathyroid hormone-related peptide, and tumors with a more proliferative phenotype had higher levels of parathyroid hormone-related peptide. Although benign lesions such as enchondromas and osteochondromas had low levels of parathyroid hormone-related peptide, malignant neoplasms such as extraskeletal myxoid chondrosarcomas, dedifferentiated chondrosarcomas, and mesenchymal chondrosarcomas expressed high levels of parathyroid hormone-related peptide. Parathyroid hormone-related peptide expression correlated with grade of malignancy in chondrosarcoma. Although there were highly significant differences between Grade I chondrosarcoma versus Grade II and Grade III lesions, the difference between Grade II and Grade III chondrosarcomas approached significance. Parathyroid hormone-related peptide may represent a new tumor marker with potential diagnostic use in classifying cartilaginous neoplasms.