Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells in the bone marrow leading to tumor growth, anemia, immune suppression, and myeloma bone disease. We are interested in understanding the role of ncRNAs in the pathogenesis of MM and myeloma bone disease. Previous studies have shown that miR-138 is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and inhibiting its function enhances bone formation. We have explored the role of miR-138 in myeloma bone disease and showed that inhibition of miR-138 results in enhanced osteogenic differentiation of MM-MSCs in vitro and increases the number of endosteal osteoblastic lineage cells and bone formation rate in mouse models of myeloma bone disease. In addition, we are investigating the biological functions of selected lncRNAs associated with the pathogenesis of MM.