It has been shown that the Hdmx gene is amplified in a subset of gliomas, but thus far, no data are available on HDMX protein expression in tumor cells. We now report that a significant fraction of tumor cell lines expresses increased HDMX levels compared with normal cells; in general, HDMX expression in these tumor cell lines correlates with the presence of wild-type p53. Analysis of tumor material showed that high HDMX expression is not a result of cell line establishment. Interestingly, several cell lines express alternative, shorter HDMX proteins. These results suggest that deregulated expression of HDMX plays a role in carcinogenesis as an alternative way to inactivate p53.