The histological distinction between benign and malignant phyllodes tumors (PT) is often difficult and arbitrary. We analyzed clinical, histological features and expressions of Ki-67 and p53 using immunohistochemistry and estimate its significance in assessing the grade of malignancy and in predicting the clinical behavior of these tumors on 20 cases of PT of the breast (11 benign, 3 low-grade malignancy and 6 high-grade malignancy). Statistically significant differences between benign, low-grade malignant, and high-grade malignant PT by size of tumor, cellular atypism, stromal cellularity, margin of tumor, and number of mitotic figures. The mean labeling index (LI) of Ki-67 in high-grade malignant PT (9.6±9.6) was three-fold higher than that in benign PT (2.7±2.2), but this difference was not statistically significant (P=0.074). None of the benign PT were positive for p53, whereas 2 of 3 low-grade malignant and 3 of 6 high-grade malignant PT were positive for p53. Statistically significant differences in the pattern of p53 expression existed among the benign, low-grade malignant, and high-grade malignant lesions (P=0.018). Ki-67 LI and p53 expression were associated with numbers of mitotic figure, but were not associated with metastasis (P=0.546 and 0.216).