© 2021 Elsevier B.V.Objectives: Intramammary mass lesions are reportedly present in up to 5.8% of all contrast enhanced CT-examinations of the female chest. We aimed to assess whether their biological relevance can be estimated using spectral CT-datasets. Methods: In this bicentric retrospective study patients with breast masses visualized on spectral CT-examinations from 07/2017 to 06/2019 were included. Lesions were characterized as malignant or benign based on histology and/or a stable follow-up of >2 years. Conventional CT-images, iodine density-maps, virtual monoenergetic-images (40 keV, 100 keV) and Zeffective-maps were evaluated by two independent readers. Statistical analysis derived from the Regions of interest (ROIs) was done by calculating the Areas under the Receiver operating characteristic (ROC) curve (AUC) and Youden-indices. Results: 106 breast masses (malignant/benign: 81/25, 76.4%/23.6%) were included. The mean AUCs of the variables “iodine content” (reader 1/2:0.97;0.98), “monoenergetic curve-slope” (0.97;0.96) and “Zeffective” (0.98;0.98) measured in the target lesions (TL) showed superior results compared to those derived from the variable “density” (0.92;0.93) (p < 0.001). The ratios “TL to aorta” calculated for the variables “iodine content”, “monoenergetic curve-slope” and “Zeffective” showed superior results compared to normal breast tissue and muscle (p < 0.001). The optimal cutpoint for the “iodine content” in the TL was 0.7–0.9 mg/ml (sensitivity 96.6%, specificity 91.7%). The best diagnostic results were achieved by normalizing the iodine content in the TL to that in the aorta (optimal cutpoint 0.1, sensitivity 95.5%, 98.9%, specificity 91.7%). Conclusions: Our preliminary results suggest that spectral CT-datasets might allow to estimate the biological dignity of breast masses detected on clinically indicated chest-examinations.