We examined Ki-67, p53, p21, and p27 immunolocalization in 43 cases of apocrine lesions of the breast and correlated these findings with histologic parameters to understand their biologic significance. Twenty cases were benign, 1 case was borderline, and 22 cases were diagnosed as malignant, including 9 intraductal and 13 invasive apocrine carcinomas. Both the ratio of Ki-67-positive cases (17 of 21 [88.9%] versus 1 of 19 [5.3%]; P < .001) and the Ki-67 labeling index of positive cases examined (15.0% versus 2.7%; P < .005) were significantly higher in malignant than in benign apocrine lesions. None of the benign or borderline cases was immunohistochemically positive for p53, but 15 of 22 malignant cases (68.2%) demonstrated p53 (P < .001). In addition, the ratio of p53-positive cases was significantly higher in high nuclear grade cases (11 of 13 [84.6%]) than in intermediate nuclear grade cases (4 of 9 [44.4%]; P < .05). P53 immunoreactivity was also positively correlated with the nuclear grade of carcinoma cases examined in this study. Neither p21 nor p27 demonstrated any correlation with histologic parameters or findings of the apocrine lesions. Results of these studies suggest that Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions.