Hairy-cell leukaemia (HCL) has long been recognized as distinct from other chronic B-cell malignancies, but several questions remain unanswered. What is the HCL cell of origin? Why does HCL lack the hallmarks of most mature B-cell tumours (for example, chromosomal translocations and consistent lymph node involvement) and show unique features like 'hairy' morphology and bone-marrow fibrosis? Gene-expression profiling and other studies have recently provided new insights into HCL biology and have the potential to affect clinical practice.