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The objective of the present study was to evaluate the diagnostic efficiency of ultrasound (US) and magnetic resonance imaging (MRI) in the diagnosis and differential diagnosis of mammary duct ectasia (MDE) and breast cancer. This retrospective study was performed on 35 patients with MDE and 105 patients with breast cancer using US and MRI. Imaging features, semi-quantitative and quantitative parameters were analyzed to determine their diagnostic value for MDE and breast cancer. The average age of patients with breast cancer was increased compared with that of patients with MDE. There were no significant differences in local packages with or without tenderness ratio (P=0.259) and grade of color Doppler flow imaging (P=0.273) between the two groups. However, the morphological changes were significantly increased in breast cancer compared with MDE. In addition, there were significant diagnostic differences in US and MRI between breast cancer and MDE, including resistance index, US elastography, time-signal intensity curve, apparent diffusion coefficient, early-stage enhancement ratio, peak-of-enhancement ratio and Tpeak (P<0.05). However, there were no observable significant diagnostic differences between US, MRI and US with MRI for MDE and breast cancer (P=0.103, P=0.263 and P=0.403 respectively). Diagnosis of MDE and breast cancer requires full evaluation of multiple parameters and morphological changes of US and MRI to increase the diagnostic efficiency. US, MRI and US with MRI were all of diagnostic value for MDE and breast cancer, while US with MRI had the highest efficacy.