Purpose: Increased bone resorption is a hallmark of multiple myeloma and a result of excessive osteoclast activation. Recently, the receptor activator of NF-κB ligand (RANKL) was found to be the critical factor for osteoclastogenesis. Studies showed that myeloma cells induce RANKL expression in bone marrow stromal cells, but it remained a controversy whether myeloma cells directly express RANKL. Methods: Therefore, we analyzed the expression of RANKL mRNA in freshly isolated CD138 positive plasma cells from patients with multiple myeloma and osteolytic bone lesions, using three different primer pairs against human RANKL. Results: RANKL mRNA could be detected in bone marrow plasma cells from myeloma patients with osteolytic myeloma bone disease. Conclusions: These findings show that myeloma cells directly express RANKL and indicate that specific blockade of RANKL may be an effective treatment for myeloma bone disease.