OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma (Peri-PM) and ductal carcinoma in situ of the breast (DCIS), and further explore some molecular mechanisms of the canceration of Peri-PM.METHODS Imunohistochemistry was used to examine the expression of E2F-1, Rb and ER in 60 Peri-PM, 60 Peri-PM with atypical ductal hyperplasia (Peri-PM with ADH) and 60 DCIS. Normal breast tissues were selected as a control group.RESULTS Based on immunohistochemical staining, the positive rate of E2F-1 expression in Peri-PM, Peri-PM with ADH and DCIS was 21.7%,46.7% and 78.3% respectively. The positive rate of Rb expression was 83.3 %, 53.9% and 21.7% and the ER expression was 86.7%,61.7% and 55.0%.Significant differences were found among the 3 groups (Peri-PM, Peri-PM with ADH and DCIS) (P＜0.05). Significant differences existed between any 2 groups (P＜0.05) except for the rate of ER positive expression comparing Peri-PM with ADH verus DCIS (P＞0.05). The expression of E2F-1 was negatively correlated with ER and Rb, and at the same time the expression of ER was positively correlated with Rb. Following the degree of breast epithelial hyperplasia involved and its development into carcinoma, the positive rate of E2F-1 expression displayed an elevating tendency, but that of Rb and ER expression showed a tendency to decline.CONCLUSION The interaction of the 3 indexes studied may play an important role in the conversion of precancerous lesions to early in situ breast carcinoma, and the evaluation of these indexes might provide a valuable basis for screening high-risk cases of Peri-PM.