Hypercalcemia may occur as a complication of haematological malignancies, in association with solid tumors with bone metastases, and with solid tumors in the absence of bone metastases. The latter syndrome, known as the humoral hypercalcemia of malignancy (HHM) shares many features with primary hyperparathyroidism. A parathyroid hormone-related protein (PTHrP) has been identified, isolated and cloned, which is most likely responsible for the calcium disturbances in HHM, PTHrP is a previously unrecognized hormone which has limited amino-terminal sequence homology with PTH and is the product of a separate gene. Tissue localization studies have identified PTHrP in squamous cell carcinomata, renal cortical carcinomata, in a proportion of breast cancers and in adult T-cell leukemia/lymphoma. In normal tissues, PTHrP has been immunohistochemically localized in keratinocytes, placenta and fetal parathyroid glands. In addition to its role in mediating hypercalcemia in cancer, PTHrP is likely to have an important endocrine role in the fetus, and perhaps a paracrine function in several organs.