Postmenopausal bleeding can be the result of numerous etiologies including endometrial carcinoma, vaginal atrophy, and endometrial polyps. Manifestation of a hematologic disease, such as acute myeloid leukemia (AML), is a rare occurrence. A 65-year-old woman with pancytopenia and postmenopausal bleeding was diagnosed with AML. Endometrial biopsy following dilation and curettage of the uterus revealed extensive mononuclear cell infiltrate consistent with AML. The patient was a poor surgical candidate and subsequently underwent treatment with chemotherapy, hormonal therapy, pelvic radiation, and uterine artery embolization to control her vaginal bleeding. A multi-disciplinary approach is necessary for treatment of post-menopausal bleeding resulting from AML infiltration of the endometrium.