The ivory vertebra sign seen on a standard radiograph of the spine should prompt investigations for a cause, which is most likely to be a bone metastasis, a lymphoma, or Paget’s disease of bone. A diagnosis of idiopathic ivory vertebra can be given if no cause is identified. We report an unusual case of ivory vertebra sign that was due to systemic mastocytosis and improved with specific treatment. Although osteoporosis is the most common bone abnormality in systemic mastocytosis, an isolated sclerotic or lytic lesion may be found. The ivory vertebra sign should not be considered idiopathic until tests are done for mastocytosis, particularly given the availability of effective treatments.