Parathyromatosis, consisting of hyperfunctioning parathyroid tissues scattered throughout the neck, is a rare cause of recurrent hyperparathyroidism after parathyroidectomy. Medical management of patients with parathyromatosis usually is ineffective. Repeated surgery often is necessary, but generally is unsuccessful. We describe a case of parathyromatosis as a cause for recurrent hyperparathyroidism. A 32-year-old woman with a history of end-stage renal disease on hemodialysis therapy for 13 years developed secondary hyperparathyroidism requiring subtotal parathyroidectomy. Three years later, hyperparathyroidism relapsed. A technetium Tc 99m-sestamibi scan showed remnant parathyroid tissue on the left inferior thyroid lobe. Percutaneous ethanol infusion therapy failed to suppress parathormone excess, and neck exploration was performed. Histological examination of pathological lesions confirmed the diagnosis of parathyromatosis. Despite extended resection of multiple parathyroid nodules, symptoms worsened, leading progressively to severe morbidity. Imaging studies at this point showed widespread hyperfunctioning parathyroid tissue within the neck. The patient refused a third operation; thus, we resorted to coadministration of paricalcitol, a less hypercalcemic vitamin D analogue, and ibandronate, a new-generation bisphosphonate. Parathormone secretion was suppressed partially with this regimen, even at the expense of hypercalcemia and hyperphosphatemia. Sustained normalization of hormone levels and normocalcemia were accomplished only after substitution of ibandronate for the calcimimetic agent cinacalcet. The question of whether calcimimetics may maximize the chance of complete cure of parathyromatosis, especially when surgical treatment fails or is not feasible, remains to be answered by future studies.