Full-field digital mammography (FFDM) as a new breast imaging modality has potential to detect more breast cancers or to detect them at smaller sizes and earlier stages compared with screening film mammography (SFM). However, its performance needs verification, and it would pose new problems for the development of CAD methods for breast cancer detection and diagnosis. Performance evaluation of CAD systems on FFDM and SFM has been conducted in this study, respectively. First, an adaptive CAD system employing a series of advanced modules has been developed on FFDM. Second, a standardization approach has been developed to make the CAD system independent of characteristics of digitizer or imaging modalities for mammography. CAD systems developed previously for SFM and developed in this study for FFDM have been evaluated on FFDM and SFM images without and with standardization, respectively, to examine the performance improvement of the CAD system developed in this study. Computerized free-response receiver operating characteristic (FROC) analysis has been adopted as performance evaluation method. Compared with previous one, the CAD system developed in this study demonstrated significantly performance improvements. However, the comparison results have shown that the performances of final CAD system in this study are not significantly different on FFDM and on SFM after standardization. It needs further study on the assessment of CAD system performance on FFDM and SFM modalities.