Trastuzumab is important for treatment of metastatic breast cancer patients with tumors that overexpress HER2/neu, but its penetration to the brain is poor. The aims of this study are to determine the prevalence of bone and brain metastasis during therapy, to compare the survival of breast cancer patients with brain metastasis who received trastuzumab to those patients not receiving trastuzumab, and to assess the impact of brain metastasis on the overall survival of trastuzumab patients. Of 103 patients treated with trastuzumab, 16 had brain metastasis and 43 had bone metastasis at the beginning of trastuzumab. The control group consisted of 196 patients with metastatic breast cancer who had never received trastuzumab. Six had brain metastasis and 75 had bone metastasis at the beginning of therapy. During therapy, only 9 of 60 trastuzumab patients (15%) developed bone metastasis, while 170 of 186 control patients (91%; c2 = 129.8, P < 0.0001) developed bone metastasis. In addition, 22 of 87 trastuzumab patients (25%) and 58 of 190 control patients (31%) subsequently developed brain metastasis. Control patients without brain metastasis experienced significantly better survival (median survival = 928 days) than those with brain metastasis (median survival = 639 days, c2 = 8.34, P < 0.005). There was no difference in survival for trastuzumab-treated patients if they acquired brain metastasis (median survival = 1400 days) or no brain metastasis (median survival > 2000 days, c2 = 0.12, P > 0.05). Patients receiving trastuzumab were unlikely to develop new bone metastasis but were as likely as control patients to develop brain metastasis. However, patients who developed brain metastasis experienced better survival compared with those patients with brain metastasis who never received trastuzumab.