Although molecular diagnosis in cancer has advanced over the last decades translation into successful therapies of solid cancers is lagging behind. In this chapter we will provide insights into the molecular analysis of single disseminated tumour cells (DTCs) â a cell population that comprises the founder cells of lethal metastasis. Here, recent data challenge the traditional approach of using the primary tumour as the surrogate marker for the selection of adjuvant therapies and emphasize the need to understand the biology of systemic cancer progression for personalized targeted therapies.