Background: Little information is available about the management and clinical outcome of bone metastases (BM) in breast cancer patients. Methods: We prospectively studied 459 breast cancer patients with first diagnosis of BM for at least 2 years to collect information about diagnosis, management and clinical outcome. Results: Two hundred and forty-eight patients (54%) had only BM, 86 (18.7%) had concomitant nonskeletal BM and 125 (27.2%) had previous nonskeletal BM. At enrolment, skeletal-related events were present in 132 patients (28.8%). Cancer treatments consisted of hormones (227/459, 49.5%) or chemotherapy (192/459, 41.8%). Age (≤70) and nonskeletal BM are inversely correlated with the use of chemotherapy or endocrine treatment (p < 0.0001). Bisphosphonates were used in 67.5% of the cases, alone (62.3%) or combined with other drugs. After a median follow-up of 28 months (range 2–43), 272 patients developed new metastases (59.2%), progression occurred mainly in nonskeletal sites (107/459, 23.3%), except for BM patients, who progressed prevalently at bone (69/248, 27.8%). New skeletal-related events were observed in 122 patients (26.6%). The 2-year probability for disease progression control and survival was 0.19 (95% CI 0.15–0.24) and 0.64 (95% CI 0.58–0.69), respectively. The 2-year probability for death according to the presence of nonskeletal metastases and the time of appearance (previous or concomitant to BM) was 0.74 (95% CI 0.67–0.79) for BM, 0.38 (95% CI 0.25–0.51) for previous nonskeletal BM and 0.56 (95% CI 0.46–0.66) for concomitant nonskeletal BM (p < 0.0001). Conclusions: Clinical outcome is significantly different according to the metastatic sites.