In 82 patients, a preoperative diagnosis of primary hyperparathyroidism was established by transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and 4 were members of families with multiple endocrine adenomatosis (MEA, types I and II). In 6 other hypercalcemic patients, high levels of iPTH were also found in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. A high serum level of iPTH was found in the superior vena cava of a 7th patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastases with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in the neck or mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; 3 were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver. The liver contained a large amount of iPTH. The results of these investigations suggest that venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production. Primary benign hyperparathyroidism is not uncommon in patients with cancer, and its coexistence must be recognized. High serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity. Hyperparathyroidism may be the 1st hint of a familial multiple endocrine syndrome.