We examined whether patients with both amyotrophic lateral sclerosis (ALS) and cancer differ from classical ALS patients, and whether motor neuron disease responds to oncological therapy. We analyzed clinical and immunological features of 14 patients (9 men, 5 women; mean age 65.3 years) with pure/definite ALS and cancer. Patients with solid tumor cancer and definite ALS were selected according to the E1 Escorial criteria; cases with ALS plus were excluded. Four patients had breast cancer, three lung adenocarcinoma, and three bowel tumor; hepatocarcinoma, kidney cancer, and mesothelioma were observed in one case each, and in one patient the primary tumor was unidentified. Patients' sera were examined for antinervous system antibodies by means of immunohistochemistry and western blot analysis. Of five patients who underwent surgical therapy, two worsened during the procedure, while the other three had no benefit. The remaining two patients did not improve after chemotherapy and radiotherapy. In none of our cases did the oncological disease progress. Death was a consequence of ALS in all eight patients who died. Median survival was 18 months and did not differ from that of 28 ALS patients matched for age, sex, and onset features (bulbar or spinal). Anti-nervous system antibodies were never detected. We conclude that our group of pure ALS patients with cancer do not significantly differ from patients with classical ALS. They usually die as a consequence of the motor neuron syndrome in the absence of cancer progression. To date we have not observed any response of ALS to antitumor therapy.