Preleukaemia has been identified as a clonal haemopathy in which progression to acute leukaemia involves conservation of the preleukaemic karyotype in the blast cells or the development of new abnormalities superimposed on the original clone. In this report, a case of childhood preleukaemia is presented in which two cytogenetically distinct clones developed over 2 years in a dysplastic marrow that was initially karyotypically normal. One clone with 47 chromosomes (47,XY,+21), disappeared without therapy. Predominance of the cytogenetically abnormal clone, 45,XY,-12,-17,t(12;17)(p11;q11) was associated with the development of acute myelogenous leukaemia and myelofibrosis. The development of independent clonal abnormalities in the unstable preleukaemic marrow may occur more commonly than has been previously recognized. Implications of the progression of the karyotypic abnormalities are discussed.