Introduction: Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis patients with chronic renal failure uremia. For severe SHPT, parathyroidectomy is effective. Owing to the variability in parathyroid anatomy, surgical parathyroidectomy can be complex and many patients experience recurrent SHPT, which may require repeated surgery. These cases pose significant challenges to surgeons. Case description: An elderly woman with recurrent severe SHPT was admitted to our hospital. Preoperative methoxyisobutylisonitrile (MIBI) examination found a large ectopic parathyroid gland in the superior mediastinum, and she underwent reoperative parathyroidectomy. A large parathyroid gland in the right anterior mediastinum and another parathyroid gland in the left lingual lobe of the thymus were removed. The patient had postoperative hypocalcemia that was successfully corrected with calcium supplementation via femoral vein catheterization. During the 1-year postoperative follow-up, the patient's iPTH was well controlled and her blood calcium was within the normal range. Conclusion: We report a case of parathyroidectomy to remove multifocal ectopic hyperplastic parathyroid tissue in the mediastinum. Preoperative MIBI accurately detected the lesions. Calcium supplementation via femoral vein catheterization successfully corrected postoperative hypocalcemia. Postoperative follow-up for 1 year indicated that the surgery was successful.