Current patient work-up, including conventional imaging and pathological assessment of just one single biopsy, might be insufficient to identify metastatic breast cancer patients, who possibly benefit from first-line anti-hormonal or anti-HER2 therapy. As receptor conversion of the tumor is found quite frequently and molecular heterogeneity can occur within one patient, up-to-date whole body information is necessary to determine estrogen receptor (ER) and/or human epidermal growth factor receptor 2 (HER2) receptor status and subsequently guide therapy decision. With molecular imaging via PET this information can be obtained in a non-invasive, patient friendly way. Furthermore, to improve and individualize treatment and be able to identify (new) drug targets and biomarkers, sampling of venous blood, circulating tumor cells (CTC), as well as circulating tumor DNA, microRNA (miRNA) and molecular characterization of one metastasis at the beginning and, if feasible, of an additional biopsy during therapy, is necessary.