Aim: To evaluate whether breast ultrasound (US) is routinely indicated following contrast-enhanced spectral mammography (CESM). Materials and methods: Consecutive screening and diagnostic CESM examinations with concurrent breast US were collected retrospectively (May 2012 to February 2016). Radiologists assigned a separate Breast Imaging-Reporting and Data System (BIRADS) score for CESM and for US. BIRADS scores were grouped into three categories: normal/benign appearing (BIRADS 1, 2); probably benign, short-term follow-up (BIRADS 3); or suspicious appearing (BIRADS 0, 4, 5). Patients with a suspicious-appearing lesion in either US or CESM underwent biopsy. The associations between malignant pathology with either suspicious-appearing CESM or suspicious-appearing US were calculated. The sensitivities and specificities of CESM and US were analysed. Results: Eighty-seven lesions were biopsied, 37 (43%) biopsies were malignant and 50 (57%) were benign. Although suspicious-appearing CESM was associated with malignant biopsies (p<0.0001), suspicious-appearing US was not (p=0.985). Among 37 malignant biopsies, CESM had a sensitivity of 97% (36/37 lesions), compared to 92% (34/37 lesions) with US. None of the malignant biopsies were normal/benign appearing with CESM. One case of follow-up CESM was suspicious-appearing at US and proved to be malignant on biopsy. The specificity of CESM was 40%, which was significantly higher than US at 8%. Conclusion: When CESM is suspicious appearing, subsequent US and biopsy is appropriate. With a CESM BIRADS 3, correlation with US is suggested. If the CESM is benign appearing, the routine use of US is questionable, as it may lead to unnecessary benign biopsies.