Consecutive stage II breast cancer patients (13) were treated with long-term adjuvant chemotherapy using chlorambucil. At least 3 of these patients developed acute myelogenous leukemia (AML). All 3 patients (and possibly a 4th) who developed AML were postmenopausal, received continuous chlorambucil for .gtoreq. 4 yr, had acute anemia at the time of treatment and had a wbc [white blood cell] count in the range of 2700-7700/mm3. After the chlorambucil was discontinued, the wbc count began to slowly rise and the patient developed clinical AML. In all 3 patients, the diagnosis of AML was established by pathologists on the basis of bone marrow biopsy, aspirate and peripheral smears. Each of these was subsequently reviewed by the hematologist who treated the patients for AML. Patients who have breast cancer (or any other solid tumor malignancy) are a risk to develop a 2nd malignancy. However, an increasing number of reports are appearing suggesting more than just a casual relationship between leukemia and the use of alkylating agents. This may be related to the dose and duration of therapy with these agents.