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Objective: To evaluate whether contrast-enhanced cone-beam breast CT (CE-CBBCT) features can risk-stratify prognostic stage in breast cancer. Methods: Overall, 168 biopsy-proven breast cancer patients were analysed: 115 patients in the training set underwent scanning using v. 1.5 CE-CBBCT between August 2019 and December 2019, whereas 53 patients in the test set underwent scanning using v. 1.0 CE-CBBCT between May 2012 and August 2014. All patients were restaged according to the American Joint Committee on Cancer eighth edition prognostic staging system. Following the combination of CE-CBBCT imaging parameters and clinicopathological factors, predictors that were correlated with stratification of prognostic stage via logistic regression were analysed. Predictive performance was assessed according to the area under the receiver operating characteristic curve (AUC). Goodness-of-fit of the models was assessed using the Hosmer-Lemeshow test. Results: As regards differentiation between prognostic stage (PS) I and II/III, increased tumour-to-breast volume ratio (TBR), rim enhancement pattern, and the presence of penetrating vessels were significant predictors for PS II/III disease (p < 0.05). The AUCs in the training and test sets were 0.967 [95% confidence interval (CI) 0.938–0.996; p < 0.001] and 0.896 (95% CI, 0.809–0.983; p = 0.001), respectively. Two features were selected in the training set of PS II vs III, including tumour volume [odds ratio (OR)=1.817, p = 0.019] and calcification (OR = 4.600, p = 0.040), achieving an AUC of 0.790 (95% CI, 0.636–0.944, p = 0.001). However, there was no significant difference in the test set of PS II vs III (P＞0.05). Conclusion: CE-CBBCT imaging biomarkers may provide a large amount of anatomical and radiobiological information for the pre-operative distinction of prognostic stage. Advances in knowledge: CE-CBBCT features have distinctive promise for stratification of prognostic stage in breast cancer.