We reviewed 66 phyllodes tumors of the breast from 60 patients. Our patients included 59 women and one man ranging in age from 16 to 72 years. Fifty patients presented for primary treatment of newly diagnosed breast masses, nine presented with recurrent tumors, and one presented with soft tissue metastases 9 years after bilateral subcutaneous mastectomies and multiple chest wall recurrences of phyllodes tumor. After 0.3 to 53.2 years (mean, 15.5 years) of follow-up, 26 (43.3%) patients are free of disease without recurrence, 26 (43.3%) patients are dead of other (17 patients) or unknown (nine patients) causes, four (6.7%) patients had locally recurrent tumor 0.7 to 2.9 years after lumpectomy and are free of disease 3 months to 12 years after re-excision or simple mastectomy, two (3.3%) patients are lost to follow-up, and two (3.3%) patients died with metastatic disease 1.8 and 7 years after diagnosis. Histologic features and flow cytometric analysis showed no correlation with outcome. Fifty-six breast tumors were biphasic and nine were purely stromal tumors. Twenty-six (47%) biphasic tumors showed stromal overgrowth. Tumor margins were pushing in 20 (39%) and infiltrative in 29 (61%) of 49 evaluable cases. Twenty-one tumors were highly cellular and 17 showed cytologic atypia. Necrosis was identified in 16 tumors. Mitotic rates ranged from 0/10 high-power fields to 48/10 high-power fields. Twenty-four diploid, six aneuploid, three tetraploid, and one polyploid tumor were identified by flow cytometry. S-phase fractions tended to be higher in nondiploid tumors. Neither DNA content nor S-phase fraction correlated with outcome. Our results indicate that most mammary phyllodes tumors, including purely stromal tumors, behave as low-grade, nonmetastasizing neoplasms. Neither histologic evaluation nor DNA content provides reliable clues concerning the natural history of an individual tumor.