Clinicopathologic characteristics were evaluated in 20 cases of cystosarcoma phyllodes in relation to clinical outcome. Flow cytometric DNA studies were carried out in 15 of these 20 cases. Stromal overgrowth and an infiltrating tumor border emerged as prominent histopathologic features that were associated with an unfavorable clinical outcome. Flow cytometric S fractions greater than 0.05 were associated with poor clinical outcome. There was no correlation between tumor ploidy and clinical outcome. There were no direct correlations between clinicopathologic features and flow cytometric measurements. Our data suggest that flow cytometric S fractions may be a useful predictor of clinical outcome in cystosarcoma phyllodes that can complement the traditional histologic analysis of these rare breast tumors.