The molecular genetic investigation of cancer is rapidly evolving because of ever-improving technology. Insights into cancer disease mechanisms are being elucidated using new chromosome-based biomarkers. Until recently, diagnostic and prognostic assessment of diseased tissues and tumors relied heavily on histologic indicators that permitted only general classifications into morphologic subtypes and did not take into account the alterations in individual gene expression or copy number. Genomic and expression profiling now allow the simultaneous interrogation of thousands of genes and offer unprecedented opportunities to obtain global molecular signatures of neoplastic cells in patient samples. One limitation of global profiling at the expression level is that acquisition and optimal transport of high-quality RNA is problematic because of its inherent instability in vitro. In contrast, tumor DNA is stable, relatively easy to transport, and can be obtained from archival paraffin tissue blocks. Thus, there is now a tremendous opportunity to globally profile copy number imbalances in tumors using array comparative genomic hybridization (CGH), which can identify at high resolution the presence of genomic copy number changes in constitutional or tumor DNA samples. Array CGH profiling has already allowed a deeper insight into the biology of a variety of tumor types and in the near future will undoubtedly prove to be a key technology leading to better cancer classification, prognosis, and outcome prediction.