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Parathyroid cysts account for 0.5% of parathyroid pathologies. They usually contain sky-high levels of parathyroid hormone (PTH) but are not necessarily associated with primary hyperparathyroidism (PHPT). Their origin is subject to debate. We provide evidence for a branchial origin and illustrate some potential problems they pose for targeted parathyroid surgery. The present study is a single institution retrospective study of 1702 parathyroid and 10 021 thyroid operations performed over a period of 12 years (1990−2001). Twenty-three cases of parathyroid cyst were found: three palpable neck masses, four cases associated with PHPT and 16 incidental findings at the time of thyroid surgery. Intracystic PTH measurements and immunostaining of the lining wall of the cyst were obtained in 16 out of 23 and 18 out of 23 cases, respectively. Intracystic PTH levels were elevated in 15 out of 16 cases (average 3877, range 36 000−23 pg\mL). The wall of the cyst stained positively for epithelial cuboidal cell markers (CK +ve) and negatively for PTH (PTH −ve) in 18 out of 18 cases. In only one quarter of the cases associated with PHPT was the cyst the hypersecreting gland, nevertheless it contained less than the average PTH level (1440 vs 3877) and did not take up sestamibi. Results were conflicting in the other three cases. Histological studies on the present series suggest a branchial pouch origin. Despite containing high levels of PTH, parathyroid cysts are of branchial origin and when associated with PHPT are rarely responsible for the disease. Targeted parathyroid surgery should not rely only on ultrasound and intraparathyroid PTH measurements. [ABSTRACT FROM AUTHOR]