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Background The B2 Prognostic Score (B2PS) is a clinical decision-making tool in metastatic breast cancer (MBC) that provides risk classification based on routine parameters. This study validates the B2PS in an independent series of MBC for the whole study group and for each intrinsic subtype. Patients and Methods We analyzed 641 metastasized patients, treated in 17 German certified breast cancer centers between 2001 and 2009. They were classified into low, intermediate, and high-risk groups according to B2PS. Overall survival (OS) curves for the various B2PS groups were compared with Kaplan-Meier method. Results According to the B2PS formula, 42.3% of patients were classified as low risk, 25.4% as intermediate risk and 32.3% as high risk. Intermediate- and high-risk patients had a statistically significant decreased OS compared with B2PS low-risk patients: (intermediate-risk: hazard ratio, 1.36; 95% confidence interval, 1.04-1.77; P = .023; high-risk: hazard ratio, 2.62; 95% confidence interval, 2.06-3.32; P Conclusions This study demonstrates the reproducibility of the B2PS based on routinely assessable parameters and confirms its prognostic value in an independent entire cohort of MBC as well as in the separate intrinsic subtypes. It therefore can help in counseling and individualizing the therapeutic regimens of those patients.