Pain in Amyotrophic Lateral Sclerosis is often underestimated and untreated by clinicians and few studies have investigated its specific features and impact. Pain experience was investigated with the Italian Questionnaire of Pain, together with the McGill Quality of Life Questionnaire for quality of life (QoL), at a baseline and at a 4-month follow-up. About half of ALS patients reported pain, described as nagging, sore, annoying, boring and exhausting, with periodic but enduring episodes. Pain was related with QoL and its intensity was able to predict QoL worsening. Obtained results indicate the importance of clinical investigation of pain in ALS patients and of the intervention with anti-pain treatment whenever necessary.