Loss of genetic material accumulates during tumor development as cancer cells select for the physical removal or functional inactivation of genes whose encoded proteins regulate normal cellular behavior. The hallmark indication for this type of gene, now termed a tumor suppressor gene, is a genetic event resulting in loss or deletion of chromosomal material. Position-oriented approaches have taken advantage of the intimate involvement of tumor suppressor gene inactivation through deletion to localize, identify, and demonstrate the involvement of these genes in carcinogenesis. Since deletion of genetic material exceeds genomic amplifications in most cancer types, loss of gene function appears to play a prominent role in tumor formation. However, despite the intimate involvement of tumor suppressor genes in the neoplastic process, relatively few of these genes have been identified, leaving the identity of the majority unknown. Thus, the use of position-based strategies for mapping and isolating tumor suppressor genes remains a prime tool in their identification.