Parathyroid carcinoma is a rare cause of hyperparathyroidism and an even rarer malignancy. It continues to be very difficult to diagnose preoperatively despite clues such as abnormally high PTH, symptomatic hypercalcemia, and at times a neck mass. Over the last decade, we have substantially increased our understanding of the pathophysiology of the disease thanks to recognition of the HRPT2 mutation in hyperparathyroidism-jaw tumor syndrome, which codes for parafibromin, a key protein involved in multiple cellular pathways for proliferation. This has substantially improved our ability to make the pathologic diagnosis and offers some promise of targeted therapies. This chapter reviews the classic and most current literature on the epidemiology, presentation, diagnosis, and treatment of the disease including the latest developments in immunohistochemistry, imaging, staging, medical management of severe hypercalcemia, surgical treatment, and radiotherapy.