Prospective studies of biomarker status in primary and recurrent or metastatic breast cancer have confirmed the findings of historical retrospective studies which demonstrate that for biomarkers which influence routine clinical practice, Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal growth factor Receptor type 2 (HER2), biopsy of recurrent or metastatic disease is essential not only to confirm the presence of malignancy but to guide targeted medical therapy. Historically, discordance rates for the expression of receptors between primary and metastatic tumors, though variable, may have led to suboptimal treatment for a significant proportion of patients. While changes in PR are most common, changes in ER (positive to negative or less frequently negative to positive) and the less common changes in HER2 (usually gain of HER2 amplification) influence subsequent therapy for 1 in 6 patients and may thus impact upon survival. Recognition of the potential for heterogeneity within the primary, between metastatic sites and over time requires further prospective study in breast cancer where the comparability of metastases from multiple sites and the need to biopsy successive recurrences have been less well documented. Recent prospective studies confirm the retrospective evidence that optimal patient care requires appropriate biopsy and pathological assessment of recurrent or metastatic breast cancer.