High-risk pedigrees (HRPs) are a key design in mapping rare and highly-penetrant genes in Mendelian-like diseases. However, success with the HRP design in complex diseases has been modest, in part because standard methods do not adequately address genetic heterogeneity. Novel methods are needed to re-invigorate HRP designs for gene-discovery in complex diseases. Extended high-risk pedigrees can contain sufficient meioses to gain power for gene mapping as single pedigrees; however, intrafamilial heterogeneity may still exist. To address intrafamilial heterogeneity, we expanded on the Shared Genomic Segment (SGS) method, a large pedigree mapping method that identifies subsets of cases within an extended pedigree that share segregating chromosomal regions. Here, I will describe this strategy and our application to high-risk myeloma pedigrees.