Biomarker analysis of tumors from patients with primary breast cancer has been commonplace for many years, with analysis of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status being mandatory for guiding therapy with anti-endocrine or anti-HER2 agents. As well as guiding adjuvant therapy, these same markers, but few others so far, are used to guide treatment selection for metastatic disease; although they are increasingly often measured in metastatic biopsies, their assessment in primary tumors remains the most frequent approach. Over recent years many multiparameter molecular tests have become available for breast cancer management. These are mainly aimed at establishing the risk of recurrence in patients with ER-positive disease who are due to receive standard endocrine therapy. Based on the prognosis of these patients, judgments can be made of the likely value of chemotherapy to improve that prognosis further. To date, these prognostic tests have had no applicability in metastatic disease.