A leukaemia presenting with two morphologically different blast populations failed to respond to either antimyeloid or antilymphoid treatment and showed a rapid clinical progression. Immunophenotyping provided good evidence for two blast populations, one lymphoid and the other lymphoid with granulocyte monocytic markers. Two different gene rearrangements within JH were also observed with band densities corresponding to the sizes of the two blast cell populations. A t(19; 22) translocation was observed in almost all cells at presentation one of which evolved into a subclone, becoming dominant in the terminal phase of the disease. We show here both the clonal evolution and clonal competition that occurred in this leukaemia and suggest that the potential of the tumour stem line for rapidly producing diversity was the reason for the resistance to treatment.