In 12 of 93 hypercalcemic patients with metastatic advanced breast cancer treated with tamoxifen the most common life-threatening metabolic complication of flare hypercalcemia developed. All the hypercalcemic patients had osteolytic or mixed lytic and blastic bone metastases. In patients with advanced breast cancer, hypercalcemia develops within the first few weeks of initiation of tamoxifen therapy. In our study group, calcium levels were measured frequently in both serum and urine samples by a semi-autoanalyzer and an autoanalyzer, using standard methods. Elevation of calcium levels was noticed in the tamoxifen-receiving hypercalcemic breast cancer patients, and levels returned to normal when tamoxifen was withdrawn. The median duration of flare hypercalcemia was 9 days (range, 4-16 days). The median calcium value was 13.6 mg/dl (range, 11.7-15.8). The diagnosis of tamoxifen flare hypercalcemia was based on the normal pretreatment serum or urine calcium values and the occurrence of hypercalcemia within the first few weeks of tamoxifen initiation. There are no specific treatment recommendations for hormone flare hypercalcemia, except for tamoxifen withdrawal, which is usually temporary, and the introduction of a low dose of an antihypercalcemic drug. We evaluated the effect of such a drug, gallium nitrate, on flare hypercalcemia. All the patients were treated with hydration, and 6 patients, whose calcium level was above 13.6 mg/dl, were treated with a moderate dose of gallium nitrate (200 mg/m(2) per kg) for 5 consecutive days, they achieved normocalcemia and continued with tamoxifen. The median time from hormonal drug initiation to flare hypercalcemia was 17.5 days, and median duration was 9 days. The above result indicates that the serious metabolic complication of hypercalcemia develops due to the iatrogenic effect of tamoxifen, but it can be controlled with an antihypercalcemic drug, gallium nitrate, while continuing tamoxifen therapy. It seems that the use of gallium nitrate in the treatment of flare hypercalcemia could allow safe readministration of tamoxifen and prevent premature tamoxifen discontinuance or withdrawal.