The authors studied prognostic factors in 77 patients with primary cystosarcoma phyllodes (CSP) of the breast. Median patient age was 50 years of age, and the median follow-up time was 8 years. Sixteen patients (21%) had distant metastases and subsequently died of CSP. Clinical variables such as age, symptom duration, clinical tumor size, and type of surgery were not of prognostic value. Local recurrence was more common among patients treated with breast-conserving surgery than among those treated with mastectomy. However, there was no significant difference between these two subgroups in terms of distant metastasis-free survival or overall survival. The prognostic significance of several histopathologic parameters was also assessed, e.g., stromal cellularity, stromal cellular atypism, mitotic activity, atypic mitoses, stromal overgrowth, tumor contour, tumor necrosis, and heterologous stromal elements. In a multivariate Cox analysis, the only features that were found to be independent prognostic factors were tumor necrosis (P less than 0.05) and presence of stromal elements other than fibromyxoid tissue (P less than 0.01). In summary, additional studies of prognostic factors in CSP are warranted because of the conflicting results in published reports.