Hypercalcemia is a frequent metabolic disorder in metastatic breast cancer (BC). Aim of this study was to evaluate the incidence of hypercalcemia due to PHPT in BC patients. The study group included 271 consecutive BC, mean age±S.D. 57.7±11.96 yrs. 100/271(36.9%) evaluated at different times after mastectomy (A) and 171(63.1%) before surgery (B), with no distant metastases. Age matched control group included 108 healthy women (Co) and 70 women with thyroid cancer(TC) before thyroidectomy. PTH and total serum calcium were measured in BC, Co and TC. The increment of serum calcium and PTH at the initial observation, indicated PHPT. Subjects with PHPT were selected for parathyroid surgery according to NIH consensus conference. PHPT was diagnosed in 12/271 BC(4.42%) and in none Co or TC. PHPT incidence in A was 7/100(7%). 2/7(28.6%) were submitted to adjuvant radiotherapy, 2/7(28.6%) to adjuvant chemotherapy two years before, and 4/7(57.1%) were on Tamoxifene therapy. A parathyroid adenoma was histologically confirmed in all 7 BC at surgery. The prevalence of PHPT in BC was significantly higher than in Co and TC (P=0.005, P=0.004 respectively). In the remaining 93 patients with no evidence of PHPT mean values of serum calcium (9.6±0.5 mg/dl) and PTH (38±16.4 pg/ml) were significantly greater than in both Co (PTH 27.9±10.6 pg/ml, P=0.0001; calcium 9.3±0.5 mg/dl, P=0.001) and TC (PTH 26.2±11.0 pg/ml, P=0.003; calcium 9.2±0.6 mg/dl, P=0.001). PHPT incidence in B was 5/171(2.92%), and in 2/5(40%) a parathyroid adenoma was histologically confirmed. In B mean serum PTH and calcium were similar to Co and TC. This study indicates an increased prevalence of PHPT in BC. The highest frequency of PHPT in A may be explained by the interferences of Tamoxifene or previous X-Ray adjuvant treatment on parathyroid cells activity. The significant increase of mean serum PTH and calcium levels in treated BC patients with no evidence of PHPT seems to confirm this hypothesis.