Aims/Background The clinical presentation of non-lactational mastitis (NLM) shares similarities with some symptoms and examination results of breast cancer (BC), which can lead to misdiagnosis or delayed treatment. Current studies on breast lesions mostly focus on the diagnostic performance of a single imaging technique. This study aims to construct a discrimination diagnostic model for NLM and BC based on such imaging features as ultrasound and magnetic resonance imaging (MRI) and to validate the application value of the model, assisting clinicians in improving disease diagnosis and refining medical decisions. Methods This study is a retrospective analysis. Clinical data of 108 patients suspected of NLM based on imaging diagnosis, admitted to The First Affiliated Hospital with Nanjing Medical University between May 2018 and August 2023, were collected. Among them, 94 cases were pathologically confirmed as NLM and 14 cases as BC. Univariate and multivariate logistic regression analyses were performed on the patients’ clinical data, ultrasound features, and MRI features to select the risk factors for discriminating NLM and BC, and construct a discrimination model. The discrimination performance of the model was analyzed with the receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve. Results In the NLM group, there were 24 cases of granulomatous lobular mastitis (25.53%) and 70 cases of plasma cell mastitis (74.47%). In the BC group, there were 2 cases of infiltrating ductal carcinoma, 2 cases of atypical hyperplasia, 3 cases of papillary carcinoma, and 7 cases of ductal carcinoma in situ. Age, internal blood flow, calcification, edge, enhancement characteristics, apparent diffusion coefficient (ADC) values, and time-intensity curve (TIC) type were independent factors for differentiating NLM and BC (p < 0.05). The ROC analysis showed that the area under the curve of the model for discriminating NLM and BC was 0.920. The DCA results showed that the model had high net benefits for discriminating NLM and BC. The calibration curve analysis showed that the model had good consistency with the actual diagnosis of NLM and BC, with a chi-square value of 4.545 and a p-value of 0.155 according to the Hosmer–Lemeshow test. Conclusion Age, internal blood flow, calcification, edge, enhancement characteristics, ADC, and TIC curve types are important factors in distinguishing NLM and BC, and the model based on the above characteristics to distinguish NLM and BC has a high net benefit in distinguishing the two.