Cancer arises as the result of sequential alterations in growth-controlling genes. Epigenetic factors, such as angiogenesis and surrounding micro-environment can also affect cancer initiation and progression. Tumorigenesis is accompanied by important changes in gene expression in the tumor cell as compared to its normal counterpart. The advent of powerful new techniques such as microarray technology and SAGE has allowed the study of gene expression in neoplastic cells at a scale never before accomplished. Indeed, it is now possible to efficiently measure the levels of thousands of genes expressed in normal and tumor tissues. This global knowledge of gene expression allows the identification of differentially expressed genes and, in principle, the understanding of the complex molecular circuitry regulating normal and neoplastic growth. Such studies have led to molecular profiling of tumors, which have suggested general methods for distinguishing tumors of various biological behaviors (molecular classi fication), elucidating pathways relevant to the tumorigenesis process, and identifying targets for the detection (biomarkers) and mechanism-based therapy of cancer. The next challenge will be the implementation of these breakthroughs in the clinic, as well as the extension of these paradigms to the fields of proteomics and physiomics.