Despite increasing molecular-genetic understanding of the development of malignant epithelial neoplasias, the front-line therapy for patients with carcinomas is still surgery. Because systemic adjuvant treatments such as chemotherapy or immunotherapy have had limited success and because the characteristics of systemically disseminated tumor cells can be very different from those of the primary tumor or end-stage metastasis, we have studied the evolution and progression of systemic cancer directly. We have developed techniques to detect, isolate and study genomes and transcriptomes of single micrometastatic cells present in bone marrow of carcinoma patients. The first results of our genetic analysis demonstrate that disseminated tumor cells are clonally related, indicating their selection from heterogeneous cell populations of the primary tumor. Gene expression analysis of single disseminated tumor cells revealed their engagement in specific functional activities, such as tissue invasion, proliferation and DNA damage repair. Detailed analyses of single disseminated cells will help determine which genotypes and phenotypes are selected during dissemination, which cells survive in the new environment and what governs the establishment of a metastasis. This knowledge will be useful in selectively targeting the precursor cells with adjuvant therapies long before metastatic disease is clinically evident and incurable.