Because genomic changes constantly accumulate during tumor progression, the systemic evolution of cancer cells cannot be deduced by analysis of primary tumors and their metastases. To follow the evolution of systemic breast cancer we analyzed single disseminated tumor cells from the bone marrow of patients with different stages of the disease. Disseminated tumor cells can be detected at a frequency of about one tumor cell per one million bone marrow cells by histogenetic markers, and their detection has been shown to be of prognostic relevance. After isolation of the tumor cells we amplified the genome of the single cells using a recently developed polymerase chain reaction technique. Subsequent comparative genomic hybridization revealed gains and losses of specific genomic regions. The comparison of single disseminated tumor cells isolated from patients with late-stage and early-stage disease now enables us to define differentially affected genomic regions. These regions could eventually turn out to be markers for systemically progressive disease and to identify patients that are at risk for metastatic relapse.