In recent years, CLL has been investigated through the use of several novel genomic technologies. CLL is a disease of mature B cells that is typically present in high abundance in blood; a typical peripheral blood smear is shown in the top panel. The typical source material used for these studies is primary peripheral blood CLL samples. Four main genomic approaches have been applied to this disease, including whole-exome/genome DNA sequencing, SNP arrays for copy number measurement, RNA sequencing and analyses of DNA methylation. These studies have added a substantial amount of information regarding the biology of CLL. CLL, chronic lymphocytic leukemia; LOH, loss of heterozygosity; SNP, single nucleotide polymorphism.