The development, refinement and increasingly widespread use of high-density DNA microarrays have been important responses to the explosion of sequence information produced by genome science. Principal among the application of microarrays is the large-scale analysis of gene expression, often referred to as expression profiling. The power of this application lies in its ability to determine the expression patterns of thousands of genes in a single experiment. Microarray use is becoming widespread in many biomedical research fields, including the study of carcinogenesis, in which expression profiling has found a number of important applications. Broadly speaking, these applications can be described as gene and pathway discovery, gene functional assignment, and tumor classification. A number of early gene expression studies using tumor cell lines and tumors have shown that DNA microarrays are powerful tools, both for identifying new genes and assigning roles to known genes involved in carcinogenesis as well as for classifying tumors subtypes. In this review, we describe the major types of DNA microarrays, discuss some practical considerations for their use, and present examples of how they are being applied to the investigation of cancer.