Increasing evidence indicates that tumor cell dissemination starts already early during tumor development and progression. Sensitive immunocytochemical and molecular assays allow now the detection of single circulating tumor cells (CTC) in the peripheral blood and disseminated tumor cells (DTC) in the bone marrow (BM) as a common and easily accessible homing organ for cells released by epithelial tumors of various origins. Tumor cells are frequently detected in the blood and BM of cancer patients without clinical or even histopathologic signs of metastasis. The detection of DTC and CTC may yield important prognostic information and might help to tailor systemic therapies to the individual needs of a cancer patient. A single DTC or CTC can express properties distinct from that of the primary tumor (e.g., increased rate of HER2/neu expression/amplification), and characterization of DTC/CTC could, therefore, help to identify therapeutic targets and select patients whose tumors are most likely to respond to targeted agents. Moreover, CTC measurements could be used for monitoring the efficacy of systemic therapies. Ongoing clinical trials will reveal whether changes in CTC status will be linked to clinical outcome. Here, we review the data on (i) BM as common homing organ for disseminating tumor cells and (ii) clinical studies on disseminating tumor cells that help to establish CTC/DTC measurements in clinical practice, and outline the (iii) biological characteristics of DTC and CTC.