The biological progression of chronic myeloid leukaemia is often associated with secondary cytogenetic abnormalities but the molecular mechanisms underlying this progression are poorly understood. This study explores the association of c-myc gene amplification with the progression of chronic myeloid leukaemia in fourteen individuals. Three of these cases showed amplification of c-myc during the course of their disease. Cytogenetic and molecular analysis of serial samples from some patients suggested the successive expansion of distinct clones of malignant cells. Our findings also suggest that trisomy 8 and locus amplification could represent alternative mechanisms for increasing c-myc gene dosage.