We describe the use of pamidronate to control marked hypercalcemia in an extremely premature infant with neonatal hyperparathyroidism that resulted from an inactivating mutation (R220W) of the calcium-sensing receptor. Despite improvement in bone mineralization and subsequent parathyroidectomy with normalization of the serum calcium level, the combination of chronic lung disease, osteomalacia, and poor thoracic cage growth ultimately proved fatal. Pamidronate therapy seems to be safe in the short-term and effective in helping control hypercalcemia even in the very premature infant, allowing for planned surgical intervention when it becomes feasible.