Here, the authors described the case of a 72-year-old CLL patient showing extensive lytic bone lesions at X-ray and MRI examinations, a diffuse infiltrate of small mononuclear cells with features of CLL cells (CD20+, CD23+, CD5+, CD138−) in a bone biopsy, and the presence of high levels of RANKL in plasma (888 pg/mL). Here, TNFSF11 is linked to B-cell chronic lymphocytic leukemia.