The four mechanisms by which malignant hypercalcemia can occur are: 1) direct osteolytic metastases (20% of cases), usually related to multiple myeloma and breast cancer with release of cytokines such as interleukin (IL)-1, IL-6, IL-8 and activation of nuclear factor kappa beta; 2) PTH-rP or humoral hypercalcemia (80% of cases) usually described in nonmetastatic solid tumors (bladder, breast and squamous cell) and some non-Hodgkin lymphomas; 3) ectopic PTH secretion with only a few cases reported, and 4) 1,25(OH)2D3 secretion that accounts for less than 1% of cases [4,5,12,13]. The gene discussed is PTH; the disease is plasma cell myeloma.