The T-cell leukaemia/lymphoma 1 (TCL1)-family oncoproteins augment AKT signal transduction and enhance cell proliferation and survival. Chromosome rearrangements, faulty developmental silencing and Epstein-Barr virus infection appear to dysregulate the expression of TCL1-family genes, provoking several important types of lymphocyte cancer. A key role for TCL1 proteins in cell transformation has been established in studies of transgenic mouse models, which develop a unique spectrum of T- and B-cell malignancies. How TCL1 proteins are regulated and dysregulated, how they promote transformation and the potential for therapies modelled on TCL1 interactions have important implications for understanding and treating lymphocyte cancers.