Cramp-fasciculation syndrome (cramp-FS) is an ill-defined condition with uncertain clinical limits. We studied a 55-year-old man with progressively more severe, widespread fasciculations and cramps during a six-year period. Mild progressive lower motor neuron loss, shown by MUNE and multiMUP analysis, developed during the four years after onset, which stabilized during a further 2-year follow-up. Cramp-FS is generally a benign syndrome, probably with several causations. Our patient developed a limited form of anterior horn cell degeneration perhaps representing a syndrome transitional with amyotrophic lateral sclerosis. Cramp-FS merits more detailed study.