Background: A positive margin status after breast conserving surgery (BCS) is one of the strongest predictors of local recurrence of intraductal and invasive carcinoma. As much as 20-50% of all patients with BCS need to undergo a second operation in order to receive free margins. In this study we tested the clinical performance of Margin Probe (Dune Medical Devices), a novel device for intraoperative margin evaluation. Methods: A prospective clinical trial was performed: The device was applied to 150 lumpectomy specimen from consecutive patients with BCS treated during the first three months in 2013. The re-excision rate was compared to the re-excision rate of a historical group of 156 patients treated with BCS during the first three months in 2012, without the application of the device. We analyzed whether Margin Probe is affected by tumor morphology, grading, size of the tumor, breast density, age, body-mass-index or the use of wire-marker. Results: Due to the application of Margin Probe the re-excision rate decreased significantly by 51% from 39.7% to 14.6%. In the subgroup of intraductal carcinoma (DCIS) the re-excision rate was reduced about two thirds from 66.7% to 23.1%. In the subgroup of invasive lobular carcinomas the re-excision rate decreased from 37.0% to 19.0%. Margin Probe results are not affected by grading, tumor size, breast-density, age, body-mass-index or wire-marker application. Conclusion: Margin Probe is an effective tool for detection of positive margins during BCS and significantly decreases the re-excision rate. It is not limited to invasive carcinoma but also detects involved margins in DCIS as well as in invasive lobular carcinoma. It does not interfere with any of the factors we examined. Citation Format: Jens Uwe Blohmer, Julia Tanko, Ragna Voelker, Julia de Grahl, Jessica Gross. Margin Probe device is able to reduce re-excision rate of breast conserving surgery in invasive and pre-invasive breast cancer independent from any patient or tumor related factors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-06.