Between 1974 and 1986, 1036 patients with operable breast cancer were treated with doxorubicin-containing combination chemotherapy regimens. Of these, 44 patients had bilateral breast cancer prior to initiation of adjuvant therapy (prechemotherapy) and 17 patients developed primary breast cancer on the contralateral side during or after completion of adjuvant therapy (postchemotherapy). The objectives of the study were twofold: to determine the incidence of bilateral primary breast cancer and to determine the effect of second primary breast cancer on prognosis of patients treated for disease in the contralateral breast. The estimated disease-free and overall survival of patients with prechemotherapy bilateral disease was similar to the patients with unilateral breast cancer. Four hundred eight patients received tamoxifen in addition to combination chemotherapy during adjuvant therapy. The incidence of contralateral breast cancer at 2 years in patients treated with tamoxifen was 0.4% in comparison to 0.8% in patients treated with chemotherapy alone. Time to development of second breast cancer in patients treated with or without tamoxifen was not significantly different (p = 0.41). We conclude that patients with bilateral breast cancer have a prognosis similar to that of patients with comparably staged unilateral disease. Although the rate of bilateral disease observed among patients treated with adjuvant chemotherapy and tamoxifen was somewhat lower than for those receiving chemotherapy only, the difference was not statistically significant.