We report a case of water-clear cell adenoma associated with primary hyperparathyroidism. A 59-year-old woman with a history of renal stones and bone fracture was referred for investigation of hypercalcemia and an elevated serum parathyroid hormone level. Skeletal X-rays showed osteopenia and ultrasound showed enlarged tumors in both sides of the inferior thyroid region. Computed tomography demonstrated a tumor in the posterior aspect of the left thyroid lobe but no lesion in the right aspect of the neck. Grossly, we found a 500 mg left lower parathyroid gland (PTG) and a 100 mg right lower PTG. Histologically, the left lower PTG comprised mainly water-clear cells (WCCs) containing numerous vacuoles. Chief cells were dispersed among the WCCs, but the right lower PTG showed normal parathyroid tissue. Several investigators have speculated that WCCs are derived from chief cells, and we diagnosed WCC adenoma. Following this case report, we review the relevant literature.