Piriformis syndrome (PS) is a rare condition characterized by pain and paresthesia of the buttock, often radiating to the posterior thigh. A patient with sciatica that was clinically suspicious for PS, underwent diagnostic work-up. A diagnosis of diffuse large B-cell lymphoma with neurolymphomatosis (NL) was made. To our knowledge, this is the first report of NL presenting as PS. NL is a possible cause of secondary PS.