Background: Multiple myeloma (MM) is a common hematologic malignancy. Immunomodulants, inhibitors of proteasome and monoclonal antibodies represent the standard of care regimens. Neurologic complications could occur in MM patients, both related to the disease or to the therapy. Posterior reversible encephalopathy syndrome (PRES) is a rare disease occurring with a several neurologic symptoms (seizures, headaches, visual loss and confusions) and characterized by typical imaging. It has been described in patients affected by malignancies but only few cases have been reported in MM patients on treatment. Case Report: We herein report the case of a 71 year-old woman with relapsed-refractory micro-molecular MM on treatment with immunomodulants who developed a clonic-tonic seizure during hospitalization for acute kidney failure. The brain computed-tomography (CT) scan and the magnetic resonance imaging (MRI), performed after the event, showed pathologic variations of cortical and subcortical signal of posterior cerebral regions. These findings were considered to be consistent with PRES. The cerebral lesions gradually disappeared, due to supportive therapy. The patient died to hematologic disease progression few months later. Conclusion: The pathophysiology of PRES is still unclear. Further studies are warranted to better understand its relation with multiple myeloma on treatment.