Predicting the biologic behavior of cystosarcoma phyllodes of the breast by histopathologic examination has been difficult. Flow cytometric DNA and cell cycle analysis was performed for 30 patients with cystosarcoma phyllodes of the breast to determine its potential prognostic utility. Traditional histopathologic parameters and the patients' clinical outcome with a minimum follow-up period of at least five years were also analyzed. Of all the variables examined, DNA ploidy, proliferative index, number of mitoses, and tumor margin were significantly associated with an adverse clinical course. Multivariate regression analysis of the authors' data showed that DNA content was a significant predictor of the patients' clinical outcome. The authors conclude that the DNA ploidy study is a useful, objective adjunct to the clinicopathologic assessment of cystosarcoma phyllodes of the breast.