Blood-borne tumour cell dissemination to distant organs can start early in cancer patients and micrometastatic spread of cancer cells is usually undetected by current imaging technologies. Therefore, sensitive methods have been developed to detect circulating tumor cells (CTC) in the peripheral blood and disseminated tumour cells (DTC) in the bone marrow at the single cell level (Alix-Panabieres et al, ARM 2012). Interestingly, the bone marrow seems to be a common homing organ for cells derived from various epithelial tumours including breast and prostate cancer (Braun et al., NEJM 2005; Koellermann et al., JCO 2008). However, a significant fraction of DTC remain over years in a “dormant” stage, and little is known about the conditions required for the persistence of dormancy or the escape from the dormant phase into the active phase of metastasis formation (Pantel et al., Nat Rev Cancer 2008, Uhr & Pantel, PNAS 2011; Lu et al., Cancer Cell 2011). Sequential peripheral blood analyses, however, are more convenient for patients than BM analyses and many research groups are currently assessing the clinical utility of CTC for assessment of prognosis and monitoring of systemic therapy (Riethdorf et al., CCR 2010). There is an unmet need for biomarkers for real-time monitoring of the efficacy of systemic adjuvant therapy in individual patients. The monitoring of CTC as “liquid biopsy” will provide new insights into the selection of tumor cells under biological therapies. CTC analyses are therefore incorporated into many current clinical trials testing new anti-cancer agents as companion diagnostics. However, current CTC assays need to be improved: CTC undergoing epithelial-to-mesenchymal transition may escape detection by epithelial markers (Bednarz et al., CCR 2010; Joosse et al, CCR 2012) and benign inflammatory bowel diseases release epithelial cells into the blood that may lead to false-positive findings (Pantel et al., Clin Chem 2012). Interestingly, cell-free nucleic acids released by CTC might become valuable biomarkers of micrometastatic disease in the future (Schwarzenbach et al., Nat Rev Cancer 2011). In conclusion, molecular characterization of DTC and CTC opens a new avenue for detecting, understanding and fighting early metastatic spread of tumour cells with important implications for future therapies.