We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the χ(2) test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was associated with poor progression-free survival compared with low expression (PNotch1 = 0.000, 40.3 vs 48.9 months; PEZH2 = 0.000, 40.2 vs 49.9 months). Moreover, we found that high Notch1 and EZH2 expression was associated with poor overall survival compared with low expression (PNotch1 = 0.000, 51.2 vs 56.2 months; PEZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2 coexpression contributes to the progression and prognosis of breast invasive ductal carcinoma.