Analysis of genetic abnormalities in tumors is becoming increasingly important in tumor pathology. Techniques available for this purpose include DNA cytometry, tumor cytogenetics (TC), in situ hybridization (ISH), and the microsatellite assay (eg, for the analysis of loss of heterozygosity [LOH]). All of these techniques have certain advantages and disadvantages. The latter make them less suitable for a detailed (eg, DNA cytometry is too crude) and extensive (eg, TC is too laborious, and ISH and LOH too specific) evaluation of the genetic changes throughout the whole genome of tumors in the pathology laboratory. The authors discuss a recently developed molecular cytogenetic technique called comparative genomic hybridization (CGH), which has distinct advantages over the other techniques. Using only a small amount of DNA, CGH can, in a single experiment, provide detailed information on gains and losses of genetic material in a tumor, throughout the whole genome. In short, tumor DNA is labeled with a green fluorochrome, mixed with red labeled normal (diploid) DNA, and hybridized to normal metaphase preparations. The green and red labeled DNAs compete for hybridization to the chromosomes. The green-to-red fluorescence ratio on the chromosomes is a measure of underrepresentation or overrepresentation (loss or gain, respectively) of genetic material of the tumor. CGH has already been applied to tumor cell lines and on fresh or fresh frozen tissues from several types of malignancies, and has revealed chromosomal regions involved in amplifications and deletions that were previously unsuspected. Another important advantage of CGH is its applicability to paraffin-embedded archival material. This application allows analysis of many tumors that are pathologically well characterized and of which the clinical outcome is known. CGH is, therefore, an important new tool in the study of cancer development and perhaps prognosis.