We performed a detailed retrospective analysis of 25 patients treated primarily at Northwestern Memorial Hospital, Chicago, for cystosarcoma phyllodes. Histopathological evaluation correlated well with malignancy, but clinical suspicion did not. Pathological studies indicated that high-grade tumors, necrosis, infiltrating margin, and the presence of more than one mesenchymal element were often associated with aggressive behavior. Flow-cytometric analyses of DNA aneuploidy and proliferative index supported the grading system we used, since all four malignant cases examined showed high proliferative index, and three of the four cases showed aneuploidy. None of the low-grade cases, including the recurrent ones, showed increased proliferative index or aneuploidy. We believe that flow-cytometric analysis ought to be performed on cases in which there is doubt regarding the potential malignancy.