Spinal cord compression (SCC) often presents a similar clinical picture to amyotrophic lateral sclerosis (ALS). An early differential diagnosis is important because SCC is a potentially treatable clinical disorder. We carried out a longitudinal study of 43 patients with an initial diagnosis of ALS, in order to ascertain the percentage of patients with SCC, and to evaluate the usefulness of somatosensory evoked potentials (SEPs) in early diagnosis. Thirty-three patients had a final diagnosis of ALS and 8 of SCC. SEPs central conduction was abnormal in 3 ALS and 7 SCC patients, respectively (Fisher exact test, p < 0.05). We concluded that SEPs investigation is useful in the differential diagnosis between ALS and SCC patients with pure motor signs.