Computer-aided detection (CADe) devices used for breast cancer detection on mammograms are typically first developed and assessed for a specific “original” acquisition system, e.g., a specific image detector. When CADe developers are ready to apply their CADe device to a new mammographic acquisition system, they typically assess the CADe device with images acquired using the new system. Collecting large repositories of clinical images containing verified cancer locations and acquired by the new image acquisition system is costly and time consuming. Our goal is to develop a methodology to reduce the clinical data burden in the assessment of a CADe device for use with a different image acquisition system. We are developing an image blending technique that allows users to seamlessly insert lesions imaged using an original acquisition system into normal images or regions acquired with a new system. In this study, we investigated the insertion of microcalcification clusters imaged using an original acquisition system into normal images acquired with that same system utilizing our previously-developed image blending technique. We first performed a reader study to assess whether experienced observers could distinguish between computationally inserted and native clusters. For this purpose, we applied our insertion technique to clinical cases taken from the University of South Florida Digital Database for Screening Mammography (DDSM) and the Breast Cancer Digital Repository (BCDR). Regions of interest containing microcalcification clusters from one breast of a patient were inserted into the contralateral breast of the same patient. The reader study included 55 native clusters and their 55 inserted counterparts. Analysis of the reader ratings using receiver operating characteristic (ROC) methodology indicated that inserted clusters cannot be reliably distinguished from native clusters (area under the ROC curve, AUC=0.58±0.04). Furthermore, CADe sensitivity was evaluated on mammograms with native and inserted microcalcification clusters using a commercial CADe system. For this purpose, we used full field digital mammograms (FFDMs) from 68 clinical cases, acquired at the University of Michigan Health System. The average sensitivities for native and inserted clusters were equal, 85.3% (58/68). These results demonstrate the feasibility of using the inserted microcalcification clusters for assessing mammographic CAD devices.