Background: An association between primary hyperparathyroidism (PHP) and amyotrophic lateral sclerosis (ALS) has been noted; however, a causal relation between these disorders has not been confirmed. Patients/ Methods: We report five patients (three men, two women) meeting El Escorial criteria for ALS who also had PHP. In three patients, the diagnosis of PHP was made during the laboratory evaluation for motor neuron disease, and in one patient, the diagnosis of PHP preceded the onset of weakness by 5 months and in another by 2 years. Serum calcium levels in all five patients were elevated, ranging from 11.2 to 12.8 mg/dL (normal, <10.4 mg/dL), as were levels of parathyroid hormone (PTH). Results: All five patients underwent parathyroid adenoma resection with subsequent normalization of serum calcium and PTH levels. Each patient had progressive weakness resulting in death 1 to 3 years following parathyroidectomy. Conclusion: Resection of parathyroid adenomas in patients meeting El Escorial criteria for ALS did not alter the course of ALS. PHP and ALS appear to be coexisting but unrelated disorders.