Neuromyelitis optica (NMO) is an autoimmune, relapsing central nervous system demyelinating disease. There is a known association between NMO and autoimmune disease. However, cutaneous findings in these cases and in the setting of isolated NMO have rarely been described. We report the case of a 60-year-old Chinese female who presented with nonspecific cutaneous findings and acute onset paraplegia and was subsequently found to be seropositive for aquaporin-4 (NMO IgG) antibodies, consistent with a diagnosis of NMO spectrum disorder. Serologic testing prompted by history and cutaneous stigmata revealed additional humoral derangements, together suggestive of an overlap syndrome with features of amyopathic dermatomyositis, rheumatoid arthritis and lupus erythematosus. We review the existing literature on the cutaneous manifestations of this entity. Awareness of the cutaneous signs and heralding symptoms of this devastating neurologic syndrome by dermatologists will ensure prompt diagnosis and initiation of treatment that can minimize neurologic sequelae.