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Background: Digital breast tomosynthesis (DBT) is a promising new technology. Some experimental clinical studies have shown positive results, but the future role and indications of this new technique, whether in a screening or clinical setting, need to be evaluated. Purpose: To compare digital mammography and DBT in a side-by-side feature analysis for cancer conspicuity, and to assess whether there is a potential additional value of DBT to standard state-of-the-art conventional imaging work-up with respect to detection of additional malignancies. Material and Methods: The study had ethics committee approval. A total of 129 women underwent 2D digital mammography including supplementary cone-down and magnification views and breast ultrasonography if indicated, as well as digital breast tomosynthesis. The indication for conventional imaging in the clinical setting included a palpable lump in 30 (23%), abnormal mammographic screening findings in 54 (42%), and surveillance in 45 (35%) of the women. The women were examined according to present guidelines, including spot-magnification views, ultrasonography, and needle biopsies, if indicated. The DBT examinations were interpreted several weeks after the conventional imaging without knowledge of the conventional imaging findings. In a later session, three radiologists performed a side-by-side feature analysis for cancer conspicuity in a sample of 50 cases. Results: State-of-the-art conventional imaging resulted in needle biopsy of 45 breasts, of which 20 lesions were benign and a total of 25 cancers were diagnosed. The remaining 84 women were dismissed with a normal/definitely benign finding and without indication for needle biopsy. The subsequent DBT interpretation found suspicious findings in four of these 84 women, and these four women had to be called back for repeated work-up with knowledge of the tomosynthesis findings. These delayed work-ups resulted in two cancers (increasing the cancer detection by 8%) and two false-positive findings. The side-by-side feature analysis showed higher conspicuity scores for tomosynthesis compared to conventional 2D for cancers presenting as spiculated masses and distortions. Conclusion: Tomosynthesis is a promising new technique. Our preliminary clinical experience shows that there is a potential for increasing the sensitivity using this new technique, especially for cancers manifesting as spiculated masses and distortions. [ABSTRACT FROM AUTHOR]