We show that in a series of eight breast cancer cell lines, a direct relationship exists between the overall DNA demethylation and the percentage of rearranged chromosomes, except for cell lines with a highly rearranged genome which can be weakly demethylated. A real time fluorescent detection method was used to quantify by reverse transcription-PCR the expression of the DNA methyltransferase 1 and of the newly discovered DNA demethylase. The overall DNA methylation status seems to result from a complex interplay between the expression of these two genes. Our results suggest that in these tumor cells, the overall DNA demethylation is implicated in one of the mechanisms at the origin of the genome instability and that besides the role of the DNA methyltransferase 1, that of the DNA demethylase may be essential in the control of DNA methylation.