As in all malignancies, the biology of HCL reflects both the behaviour of the malignant cells (hairy cells) themselves and their two-way interaction with the microenvironment. However, the tissue interactions of HCs are particularly striking and involve extensive remodelling of bone marrow, spleen and liver, with relative sparing of lymph nodes. The mechanistic basis of this remodelling is now largely understood and is described herein. Regarding HCs themselves, they are late clonal B cells which have often undergone heavy-chain-isotype class switching and whose VH genes are usually mutated. HCs are highly activated cells in which a number of signalling pathways are constitutively active. This activation determines many of the specific features of HCs, but its cause remains unknown.