Background: Prior head and neck irradiation is a known risk factor for hyperparathyroidism. It is not clear whether irradiation for breast cancer, which may expose the neck to radiation, is also a risk factor for hyperparathyroidism. The present study analyzes the association between the side of radiation to the chest following breast surgery and the side of subsequent parathyroid adenoma development. Methods: We analyzed a prospective database of 1,428 consecutive patients who underwent parathyroidectomy at our institution between November 2000 and August 2010. Patients who had previously undergone breast surgery were identified. Patients with multigland disease were excluded. Patients with bilateral breast surgery were counted as having had two separate procedures; one on each side. Patients who had radiation therapy following breast surgery (RadRx) were compared to those who had breast surgery without radiation treatment (No RadRx). Results: A total of 146 breast procedures were performed in 121 patients. Forty procedures were in the RadRx group versus 106 cases in the No RadRx group. Patients with radiation therapy were older (68 ± 1.8 years versus 63 ± 1.2 years; P = 0.02) and had higher preoperative calcium levels (11.3 ± 0.1 mg/dl versus 10.9 ± 0.1 mg/dl; P = 0.001). However, there was no significant difference in either parathyroid hormone (PTH) level or gland weight. The latency period between breast irradiation and parathyroid surgery was 8 ± 0.9 years. Interestingly, the side of radiation therapy was associated with the side of the parathyroid adenoma in 76% of cases, compared to only 44% in those who had breast surgery without radiation exposure (P = 0.0004). Conclusions: The present study demonstrates that, similar to prior head and neck radiation, prior breast irradiation correlates with the development of parathyroid disease. Specifically, there is a strong correlation between the side of the radiation therapy and the side of a subsequent parathyroid adenoma. Breast irradiation should therefore be considered a risk factor for the development of parathyroid adenomas. © 2011 Société Internationale de Chirurgie.