Blood-borne distant metastasis is the leading cause of cancer-related death in breast cancer. The onset of this fundamental process can now be assessed in cancer patients by using ultrasensitive immunocytochemical and molecular assays able to detect even single metastatic cells. To date, clinical studies with large study populations, validated immunoassays, and adequate follow-up time provide evidence for the independent prognostic value of the presence of disseminated tumor cells in the bone marrow. At present, bone marrow evaluation may therefore be considered a diagnostic tool for improved risk assessment with regard to distant relapse and death, especially among potentially curable breast cancer patients. Except for promising pilot studies, no data are available to support the immediate use of bone marrow evaluation for treatment monitoring in order to enable the prediction of response to adjuvant therapy.