AbstractBackground and ObjectivesOsteolytic bone tumors produce intercellular signaling proteins that regulate bone remodeling by altering the rates of osteoclast and osteoblast differentiation and activity. This report examines osteolytic bone tumor expression of receptor activator of nuclear factor B‐ligand (RANK‐L), a cytokine that is arguably the most critical regulator of osteoclast differentiation and activation.MethodsThis prospective immunohistochemical study examined RANK‐L expression in frozen tissues from sixteen surgical specimens of patients who underwent surgery for the treatment of osteolytic bone tumors between 1999 and 2000.ResultsRANK‐L was positive in 13 of the 16 cases. Primary benign bone tumors, primary malignant bone tumors, and metastasis to bone were positive for RANK‐L.ConclusionsThe cells in some, but not all, osteolytic tumors produce the cytokine RANK‐L. Further study is necessary to determine in which specific tumors RANK‐L is the cytokine responsible for increased osteoclastic activity, and to develop possible therapeutic use of RANK‐L antagonists such as osteoprotegerin (OPG). J. Surg. Oncol. 2002;79:174–179. © 2002 Wiley–Liss, Inc.