During B lymphocyte maturation, a subset of B cells undergo class switch recombination (CSR), a process wherein the heavy chain constant region is changed to a different immunoglobulin isotype without introduction of variable region mutations. CSR thus allows for the production of various antibody isotypes with different effector functions. Similar to naive B cells, chronic lymphocytic leukemia (CLL) cells co-express surface immunoglobulin (Ig) M and D (IgM+IgD+), though a minority of cases express terminally differentiated isotypes. In this brief report, we discuss the capacity of CLL to undergo CSR and the relevance of CSR to the clinical behavior of CLL.