Many adjuvant chemotherapy regimens used for breast cancer include prednisone, which has the potential to cause hyperglycemia. We reviewed the results of three CALGB studies employing prednisone as part of adjuvant therapy to determine the incidence and severity of hyperglycemic complications. All treatment regimens included cyclophosphamide, methotrexate or doxorubicin, 5-fluorouracil, and vincristine in addition to prednisone. Among 1,237 evaluable patients receiving a five-drug regimen including prednisone, there were 98 patients (7.9%) who experienced any degree of hyperglycemia. Thirty patients (2.4% overall; 30.6% of those having any hyperglycemia) had severe or life-threatening degrees of hyperglycemia, including two patients whose hyperglycemia contributed directly to death. We conclude that prednisone administration as part of adjuvant chemotherapy regimens in breast cancer produces an appreciable incidence of hyperglycemia. Serum glucose levels should be monitored during therapy to help prevent the occasional severe or life-threatening episode of hyperglycemia in these patients.