A 2006 National Cancer Institute workshop on chromosomal translocations brought together laboratory, clinical, and population scientists to cross-fertilize and catalyze research on this important disease process. The deliberations revealed significant contrasts between two types of translocations that result in either deregulated expression of oncogenes or formation of novel fusion genes. The classic oncogene-activating translocation, MYC-IGH, has been elucidated in terms of molecular structure and functional consequences yet has little epidemiologic characterization. In comparison, the archetypal fusion-gene translocation, BCR-ABL, has well-described clinical manifestations but is less defined with regard to mechanism of generation. Interdisciplinary collaboration on chromosomal translocations should yield additional insights regarding their biological significance and potential as targets for intervention.