Objective To analyze the correlation of the statuses of different lumpectomy margins and the expression of estrogen receptor(ER), progestogen receptor (PR) and HER-2 in breast conserving surgery, so as to explore the suitable width for negative margin in different approximate molecular subtypes of breast cancer. Methods A total of 80 patients who met the standard of breast conserving therapy were included in our study.The width of the surgical margin was 2 cm.Modified radical mastectomy was performed when the intraoperative frozen section examination showed positive margins.Margins of different widths (5 mm, 10 mm, 15 mm, and 20 mm) at six directions (superior, inferior, left, right, anterior, and posterior) were examined pathologically after operation.The patients were divided into four approximate molecular subtypes according to the immunohistochemical examination of ER, PR and HER-2.The widths of negative margins in the four subtypes were analyzed statistically to select the suitable width of surgical margin for different subtypes. Results The negative rates of 5 mm, 10 mm, 15 mm, and 20 mm margin widths were 51.25%, 81.25%, 97.50% and 98.75%, respectively. The negative rates for 15 mm, 20 mm margins were significantly higher than those for 5 mm, 10 mm margins (P<0.05).The negative rate was 97.4% on the width of 10 mm in Luminal-A, significantly higher than that on the width of 5 mm(P<0.05) and not significantly different from that on the width of 15 mm.The negative rate was 100% on the width of 15 mm in patients with triple negative breast cancer, significantly higher than that on the width of 10 mm(P<0.05).There were no significant differences in the negative rates between different widths in both Luminal-B and HER-2+ groups. Conclusion The widths of negative surgical margins are different for different subtypes: 10 mm might be suitable for margin width of Luminal-A and 15 mm for that of triple negative breast cancer.As for Luminal-B and HER-2+ types, 20 mm or even wider margins might be suitable.