Gene amplification is an important manifestation of genetic instability in cancer. Recently, the study of gene amplification has been greatly facilitated by the development of the molecular cytogenetic techniques of comparative genomic hybridization and chromosome microdissection. We describe in this brief overview a combined approach using both techniques, which allows the identification of chromosomal regions of gene amplification and provides entry point clones for target gene identification. This molecular/cytogenetic approach consisting of chromosome microdissection and comparative genomic hybridization should be valuable in identifying novel amplified genes important in neoplastic development and progression.