Multiple myeloma (MM) bone disease is characterized by increased bone resorption and osteolytic lesions that do not heal due to a concomitant marked reduction in bone formation. MM tumor cells secrete and induce factors that increase osteoclasts (osteoclast activating factors [OAFs]) and suppress osteoblast differentiation (osteoblast inhibitors [OBIs]), leading to characteristic bone alterations that contribute to the initiation and/or progression of MM. The study reported in this issue shows that MGUS and AMM patients with high CCN1 levels in their marrow have a longer time to progression to myeloma. Similarly, MM patients with high CCN1 levels in their marrow were found to have longer progression-free and overall survival. The authors further show that mesenchymal stromal cells (MSCs) in the MM microenvironment produce CCN1, which can suppress MM cell growth and osteoclast activity and increase osteoblast differentiation, providing a potential explanation for their findings. Professional illustration by Luk Cox, Somersault18:24.