Chronic lymphocytic leukaemia (CLL) represents an abnormal clonal expansion of mature antigen-experienced CD5+ B1a cells (Chiorazzi et al, 2005), which present with a highly heterogeneous clinical course depending on associated chromosomal aberrations, somatic mutations within the immunoglobulin variable heavy chain genes (IGHV), and surface CD38 or intracytoplasmic ZAP-70 expression. Given that key signalling components of the B-cell receptor (BCR) are relevant contributors to the variable clinical behaviour of CLL (Stevenson et al, 2011) we explored the influence of functionally relevant germline CD5 variants on CLL prognosis.