Abstract: From the beginning to the end, the life of B cells is dominated by selection of the cells for expression of an appropriate antigen receptor. However, recent studies revealed that there are several diseases in the human where B cells lost their dependence on a B cell receptor (BCR). In classic Hodgkin's lymphoma, the lymphoma cells presumably derive from ‘crippled’ germinal center (GC) B cells that acquired unfavorable somatic Ig gene mutations, which often render originally functional immunoglobulin (Ig) genes nonfunctional. A peculiar situation is observed among Epstein‐Barr virus (EBV)‐infected B cells in angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD)‐type T cell lymphoma, where somatic hypermutation uncoupled from any selection for functionality of the BCR is observed in expanding clones. Clones of EBV‐harboring B cells that show ongoing hypermutation during proliferation and are Ig‐deficient in at least a fraction of cases were recently also identified in post‐transplant lymphoproliferative disorders. Hence, transformed B cells may, in particular settings, escape the normal selectional forces to express a BCR, and EBV may cause dramatic changes in B cell differentiation programs. Somatic hypermutation may be involved in lymphomagenesis by several means. Some chromosomal translocations into Ig loci likely involve DNA‐strand breaks associated with hypermutation. Moreover, by aberrant targeting of the CD95 gene, GC B cells and lymphomas developing from them may become resistant to elimination by CD95 ligand‐expressing T cells. Finally, aberrant hypermutation of multiple proto‐oncogenes appears to be a major factor in diffuse large cell lymphoma pathogenesis.