The parafibromin gene (CDC73, previously HRPT2) is frequently inactivated in malignant tumors, and loss of function mutations are identified in the germline of patients with apparently sporadic parathyroid carcinoma (as well as in other CDC73 related disorders, such as hyperparathyroidism-jaw tumor syndrome and familial isolated hyperparathyroidism). Here, CDC73 is linked to familial isolated hyperparathyroidism.