The constitutional balanced translocation (3;8)(p14.2:q24.1) has been described in a family in which a arge number of individuals developed renal cell carcinoma RCC) at an early age. The translocation event in which genes from the 3p14.2 and the 8q24.1 sites are brought in close proximity is considered a critical, initial step for the development and progression of RCC. Even though the 3p14.2 breakpoint region has been cloned, a gene has not yet been identified, which may be responsible for either the initiation or progression of hereditary RCC. As a crucial step toward cloning the 3;8 breakpoint at the 8q24.1 site, we have mapped a series of YACs which surround this region by fluorescence in situ hybridization (FISH). Three YACs have been identified that span the 8q24.1 breakpoint region. One of these YACs is approximately 180 kb in length, and has been used to initiate construction of a high resolution cosmid contig. Several cosmids have been isolated which have been positioned in relation to the 8q24.1 breakpoint region. In addition, we have positioned 26 other YACs in relation to the 3;8 translocation breakpoint. These results provide a basis for the isolation of genes surrounding 3;8 RCC translocation breakpoint region at 8q24.1.