This unit presents comparative genomic hybridization (CGH), a genome-wide screening technique for genetic aberrations in tumor samples. Specific emphasis is placed on recent applications to the analysis of murine model systems for human cancer. CGH is an invaluable tool for identifying the characteristic genetic rearrangements in these models. The authors discuss an exciting new method currently being developed, array CGH, which results in a tremendous increase in resolution. Oncogene amplifications and deletions of tumor-suppressor genes are detected on a single-gene level. Detailed protocols are supplied for CGH analysis of both human and mouse chromosomes.