This chapter discusses genetic predisposition to development of neuroblastoma, as well as the common genetic changes in neuroblastoma tumor cells. Neuroblastoma is the most common pediatric cancer and is responsible for approximately 15% of all childhood cancer deaths. It is an embryonal cancer of the postganglionic sympathetic nervous system and most commonly arises in the adrenal medulla. Germline chromosomal abnormalities have been identified rarely in children with neuroblastoma. Virtually all neuroblastoma cell lines and primary tumors with 1p deletions reported in the literature are hemizygous for a region that includes distal 1p36.2 and all of 1p36.3. The majority of 1p deletions in neuroblastomas are large, often resulting in loss of the majority of the short arm. The mechanism of deletion is complex, but frequently is the result of an unbalanced translocation with chromosome A genome-wide search for linkage has identified the short arm of chromosome 16 as likely site of a hereditary neuroblastoma predisposition gene.