Metastatic breast cancer is a major cause of death in middle-aged women. The aim of our research is studying the two routes of metastatic spread; lymphatic and haematogenous, and characterization of disseminated tumor cells in relation to patients’ outcome in clinical cohorts. Even synchronous lymph node metastases show signs of tumor progression compared to the primary tumor with implication on the individual patient’s prognosis. The evolution of the tumor is even more evident in established distant metastases and in circulating tumor cells (CTCs) in the peripheral blood. In the CTC-MBC clinical trial (Clinical Trials NCT01322893) patients with metastatic breast cancer are included and serial blood samples for enumeration and molecular characterization of CTCs using CellSearch® are collected, and serum and plasma from the same time-points are analyzed, referred to as “liquid biopsies”. A downstream method characterizing CTCs then enables real-time analysis of predictive markers.