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Background: Automated breast ultrasonography (ABUS) has the potential to be an important adjunct to mammography in women with dense breasts., Purpose: To compare reader performance and inter-observer variation of ABUS alone and in combination with mammography., Material and Methods: This retrospective study had ethical committee approval. All women gave written informed consent. One hundred and fourteen breasts in 90 women examined by digital mammography and ABUS were interpreted by five radiologists using BI-RADS categories. The 114 breasts included 38 cancers and 76 normal or benign findings. In the first reading session ABUS only was interpreted, and in the second ABUS plus digital mammography. Image interpretations were done without knowledge of clinical or imaging results. A consensus panel analyzed false negative and false positive interpretations. Reading time was recorded for one radiologist. AUC was used for performance measurement, and kappa statistic for inter-observer variability., Results: Mean size for cancers was 16.2 mm; area under the curve (AUC) values for ABUS alone and for combined reading were, respectively: reader A, 0.592-0.744; reader B, 0.740-0.947; reader, C 0.759-0.823; reader D, 0.670-0.688; reader E, 0.904-0.923; and all readers combined 0.730-0.823. The higher AUC for combined reading was statistically significant (P < 0.05) for reader B and for all readers. There was a considerable inter-observer variability. Observer agreement revealed following kappa values for ABUS alone and combined reading, respectively: reader A, 0.22-0.30; reader B, 0.33-0.44; reader C, 0.32-0.39; reader D, 0.07-0.14; and reader E, 0.34-0.43. Shadowing from dense parenchyma was the most common cause of false positive ABUS interpretations. Mean interpretation time for a bilateral normal ABUS examination was 9 min., Conclusion: Observer agreement was higher and all radiologists improved diagnostic performance using combined ABUS and mammography interpretation. Combined reading should be standard if ABUS is implemented in screening of women with dense breasts., (© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)