© 2016 The Royal College of RadiologistsAim To analyse the value of targeted second-look ultrasound and imaging-guided biopsy in high-risk young women eligible for screening magnetic resonance imaging (MRI) in a tertiary referral centre in Perth, Western Australia. Materials and methods A retrospective analysis of eligible high-risk young women who underwent screening breast MRI and targeted second-look ultrasound between June 2012 and June 2014 was performed with review of data. Results Over a 2-year period, 139 women underwent high-risk screening MRI. Of these, 30 women (with a total of 45 lesions) were recalled for targeted second-look ultrasound. Thirty-four MRI-detected lesions were identified on targeted ultrasound with 19 of them proceeding to ultrasound-guided biopsy, while the remaining 15 lesions were considered benign on ultrasound, were not biopsied, and were stable on follow-up imaging 12 months later. One lesion proceeded to an MRI-guided biopsy to confirm a benign result. Of the 11 lesions not seen on ultrasound, nine underwent MRI biopsy, one proceeded directly to hook wire localisation and excision, and one did not return for biopsy and was lost to follow-up. The overall biopsy rate was 14.4%. The cancer detection rate was 1.4%. Conclusion The results of this study indicate that targeted second-look ultrasound and ultrasound-guided biopsy is a cost-effective and time-efficient approach for MRI-detected lesions in young women at high risk of developing breast cancer. MRI-guided biopsy should be considered for ultrasonographically occult suspicious lesions as there is a low, but definite, risk of cancer.