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Purpose: To determine the added value of mammography in women with focal breast complaints and the utility of initial targeted ultrasound in this setting. Methods: Women with symptomatic breast disease who were evaluated by breast imaging (mammography/digital breast tomosynthesis and ultrasound) between January 2016 and December 2016 in the Radboud University Medical Centre were included. We retrospectively collected the following data: date of birth, indication of imaging, visibility on mammography/ultrasound, whether biopsy was taken, additional findings, BI-RADS-classification, pathology and follow-up results. Results: A total of 494 women were included (mean age 46.5, range 30 to 93). In 49 women (9.9%), symptomatic breast cancer was diagnosed, all visible during targeted ultrasound. The negative predictive value of targeted ultrasound was very high (99.8%). Additional findings on mammography were significantly more often malignant when the symptomatic lesion was also malignant (3.8% vs 70%, P < 0.05). In only one patient with symptoms caused by a benign finding, an incidental malignancy was detected on mammography outside the area of complaint (detection rate 2.2/1000 examinations). Conclusions: The contribution of mammography for cancer detection in women with focal breast complaints is very low when targeted ultrasound is performed. Additional findings are most common in patients with symptomatic breast cancer. Our results suggest that initial targeted ultrasound is a more appropriate initial tool for the evaluation of focal breast complaints. Mammography could be performed on indication only. [ABSTRACT FROM AUTHOR]