Hypercalcemia of cancer is due to secretion of substances with parathyroid hormone (PTH)-like activity from tumours of the respiratory, gastrointestinal and urogenital tract as well as hematologic malignancies and breast cancer. PTH-related Protein (PTHrP) is secreted mainly from solid tumours and it has been recently recognized as being responsible for hypercalcemia mediated primarily via an increased renal reabsorption of calcium and secondly by an increased bone resorption. PTHrP-mRNA is expressed in a variety of normal tissues and has multiple physiologic and paracrine actions. Bone resorbing factors like the cytokines-lymphokines, interleukins, prostaglandins, TNF-alpha/TNF-beta, GM-CSF/G-CSF, TGF-alpha and TGF-beta are produced by certain solid and hematologic cancers and have also been implicated in tumour-induced hypercalcemia. The recently introduced PTHrP antagonists are hopeful therapeutic measures for the future.