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Primary hyperparathyroidism commonly results from a solitary parathyroid adenoma. A water clear cell parathyroid adenoma represents a rare histological variant. This report presents the challenges of preoperative detection of a giant parathyroid adenoma, which was of the water clear cell variant. A case of severe hypercalcemia in a patient without clinical symptoms and equivocal findings on standard imaging modalities, in which the use of [ 11 C]C-Methionine PET/CT facilitated the preoperative detection of a giant parathyroid adenoma. Histopathological examination confirmed the diagnosis of a water clear cell giant parathyroid adenoma following surgical excision. These findings highlight the significance of advanced imaging techniques in the detection and management of a rare form of parathyroid adenoma., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)