Prostate cancer is a heterogeneous disease with multiple loci contributing to susceptibility. Traditionally, genome-wide scans using high-risk families have utilized stratification by number of affected individuals, family history of other cancers, or family age at diagnosis to improve genetic homogeneity. In addition to locus heterogeneity, for later onset diseases such as prostate cancer, a major limitation to mapping efforts is that key parental DNA samples are rarely available. The lack of available samples from upper generations reduces inheritance information, and as a result, the standard 10-cM genome scan does not provide full power to detect linkage. To increase the ability to find disease-associated loci, much denser genome-wide scans must be undertaken in multiple ethnic groups. In addition, new ways of defining homogenous subsets of families need to be developed.