Twenty-eight consecutive patients with breast cancer were analyzed who presented with a single brain metastasis as first site of distant metastasis. The response to surgery with postoperative radiation therapy (RT) (9 patients) and to non-surgical therapy as first-line treatment was 100% and 89% respectively with a significant difference in median recurrence-free intervals of 23 months and of 5 months respectively (p = 0.033). Retreatment of a local relapse by surgery (+/-RT, +/-chemotherapy) or by non-surgical treatment resulted in a response in 6 of the 7 operated patients and in 5 of the 6 non-operated patients with a median duration of response of 7 months (range 2-20 months) and of 3 months (range 2-4 months) respectively. The overall median survival of the 28 patients with a single brain metastasis was 16 months (range 2-39 months). The median survival in the primarily operated patients was 23 months, in the primarily not-operated group 10 months, and in the never-operated group 9 months. In comparison, the response to non-surgical treatment in 20 consecutive patients who presented with multiple brain metastases as first site of distant metastasis was 55% with a median recurrence free interval of 4 months. The median survival in this group was 4 months, which was significantly shorter than survival of patients with single brain metastasis (p = 0.0036). These results suggest that breast cancer patients with a single brain metastasis as first presentation of relapse constitute a specific subgroup with a favorable response to treatment and a long survival especially if they can be treated by surgery with postoperative RT.