A rare case of severe hypercalcemia strongly associated with Systemic Lupus Erythematosus (SLE) is reported. On admission, a young woman showed severe hypercalcemia and photosensitivity. Criteria for diagnosis of SLE were not sufficient. All causes, common and uncommon, of hypercalcemia were excluded. Radiographs of the skeleton were normal. One year later diagnosis of SLE was evident. In addition, diffuse and severe osteopenia and chest deformities had occurred. The treatment of SLE normalized persistently calcemia. Mild elevation of calcium levels occurred during flares of SLE. It has been hypothesized that hypercalcemia in patients with SLE could be caused by the presence of stimulatory anti-PTH receptor antibodies. This case report suggests that in patients with severe hypercalcemia associated with SLE early diagnosis and treatment of SLE may prevent bone loss. In these patients the prevention of severe bone damage is very important. Indeed, severe osteopenia may favour skeletal deformities and fractures; in addition it may represent a serious obstacle in using adequate doses of glucocorticoids for treatment of SLE.