A cellular phosphoprotein that binds to and inactivates p53 has recently been identified as a product of the oncogene MDM2. Amplification of the MDM2 gene was found in more than a third of sarcomas and in a subset of malignant gliomas. Despite the absence of amplification, the MDM2 gene was overexpressed in some types of leukemias and lymphomas. Overexpression was significantly more frequent in the low-grade type of B-cell non-Hodgkin's lymphoma (B-NHL) than in the intermediate/high grade types of lymphoma and the overexpression was also significantly more frequent in the advanced rather than the earlier stages of B-cell chronic lymphocytic leukemia (B-CLL) and B-NHL. This suggests that MDM2 could play a role, via the p53 pathway, in tumorigenicity and/or in disease progression in some hematological malignancies. However, in the light of our findings that, in a few cases, both the overexpression of MDM2 and mutant-type p53 was seen, it is possible that MDM2 overexpression may also promote neoplastic growth by mechanisms other than inactivation of the p53 protein.