Abstract Background: External radiation to the head and neck is a known risk factor for the development of parathyroid adenoma. But the incidence is very rare in internal radiation recipients. Here we describe a case of parathyroid adenoma after 30 years of radioactive iodine therapy for Graves’ disease. Clinical Case: A 50-year-old female presented during an annual visit with progressive fatigue, polyuria, polydipsia, nocturia, muscle weakness, and some memory impairment. She had a past medical history of Graves’ disease treated with radioactive iodine therapy 30 years ago with subsequent hypothyroidism, controlled essential hypertension, asthma, and obesity BMI 32.5 kg/m2. There was no history of nephrolithiasis, fractures, pituitary tumor, or acid reflux. Family history was noted for thyroid diseases, no calcium issues or hyperparathyroidism. Neck examination did not reveal any thyromegaly or palpable nodule. Laboratory tests showed calcium 11.4 mg/dL (8.6-10.3), ionized calcium 6.1 mg/dL (4.2-5.4), parathyroid hormone 213.9 pg/mL (12-88), total vitamin D 22 ng/mL (31-100), TSH 0.47 uIU/mL (0.34-3.00), Free T4 1.1 ng/dL (0.6-1.6), creatinine 0.7 mg/dL (0.6-1.2), eGFR >60 ml/min/1.73 m2, 24-hr urine calcium 405 mg (40-350). Bone density revealed T-score -4.9 at the lumbar spine, -2.8 at the total hip, -3.1 at the femoral neck, and -2.9 at distal 1/3 radius. Neck ultrasound showed atrophy of the thyroid gland with a lobulated hypoechoic area measuring up to 1.3 x 0.9 x 0.9 cm without internal blood flow at posterior inferior to the right lobe of the thyroid gland. Parathyroid SPECT/CT scan revealed no evidence of parathyroid adenoma. The hypoechoic lesion was suspected to be a lymph node according to imaging studies. However, according to laboratory and bone density results, we suspected primary hyperparathyroidism in which the patient required surgery due to current symptoms. The patient underwent surgery with an intraoperative finding of a nodule at the superior of the right parathyroid gland. A frozen section of the nodule was sent which confirmed parathyroid adenoma. The gland, weighted 483 mg, was removed with subsequent improvement of intraoperative parathyroid hormone level from 238.5 pg/mL to 26.5 pg/mL. Follow up calcium was at 9.5 mg/dL. The patient was supplemented with calcium and vitamin D afterward. Her symptoms improved significantly. Conclusion: Hypercalcemia in a patient with prior history of radioactive iodine therapy should raise concern for parathyroid adenoma. Imaging of the parathyroid gland should be cautiously interpreted with laboratory tests as it could be a false negative. Due to patient met criteria for surgery, the surgical approach should be pursued for both diagnostic confirmation and definite treatment. Intraoperative parathyroid hormone monitoring is beneficial in equivocal imaging and in reflecting successful resection of uniglandular disease.