Lay Summary Hodgkin Lymphoma (HL) and B precursor acute lymphoblastic leukemia (B-ALL) are common malignancies of childhood with well documented evidence of familial clustering. This familial clustering may be explained by changes in DNA which may lead to diseases that can be passed from generation to generation. However, to date little is known regarding which mutations in genes are causing HL or B-ALL within families. To better identify these genes, we have performed whole genome sequencing (WGS) on the largest group of families with a high frequency of HL or B-ALL. Having this WGS information from both affected and unaffected family members improves the possibility of finding a potential genetic basis of these important pediatric cancers of childhood within the families. Preliminary analyses of our WGS results have identified potential genes of interest, but extensive analysis is needed to interrogate coding regions, non-coding regions, copy number variants and structural variants. All findings from our families will then be validated for frequency in a sporadic cohort of patients with these diseases that have already have WGS performed and their data are available for analyses. This research is important because it provides an innovative and comprehensive approach to answering the question of what predisposes patients to the development of HL and B-ALL. The knowledge gained through this study will be invaluable as it will help us understand the origin of the disease and identify better screening, prevention and treatment for patients with HL and B-ALL.