A 41-year-old woman with SAPHO syndrome presented with numbness of her left arm followed by a generalized seizure. Computed tomography and magnetic resonance imaging of the brain revealed a small ring enhancing lesion in the right parietal lobe with adjacent meningeal thickening and enhancement. Surgical removal and histopathology showed evidence of severe chronic sterile inflammation and no malignant cell. Symptoms recurred and a lesion were again detected on radiological follow-up, but improvement occurred following treatment with antibiotics and biphosphonate, achieving a low inflammatory activity, reduction in CNS lesions and relative clinical well-being. This is a first report in literature about the central nervous system involvement in a patient with SAPHO syndrome.