A longitudinal deep-sequencing study in 12 homogeneously treated patients provides the first evidence of convergent subclonal evolution in chronic lymphocytic leukaemia (CLL) pathogenesis. The dominance of subclones harbouring distinct mutations at the same disease loci—NOTCH1 and DDX3X in one patient, and SF3B1, DDX3X and del(11q23) in another—changed over the course of disease. These findings highlight certain combinations of genetic aberrations that might confer a selective advantage for CLL-cell growth.