We describe a 64-year-old patient affected by multiple system atrophy (MSA) whose symptoms of cerebellar ataxia were temporarily markedly worsened by smoking a cigarette. Interestingly, a similar phenomenon was reported in the original description of MSA by Graham and Oppenheimer in 1969, although never again since then. Cholinergic involvement is present in MSA, as shown by recent pathological and functional neuroimaging studies. Further studies are warranted to investigate the prevalence of nicotine sensitivity in MSA and shed light on its neurochemical substrate.