Background: Clinical outcome after surgery of breast cancer needs more prognostic markers to predict currently. Cluster of differentiation 47 (CD47), due to its overexpression in various tumors and ability to inhibit phagocytosis, has been identified as a new immune checkpoint. Monocarboxylate transporter 1 (MCT1) is a protein involved in the immunomodulatory activities of the tumor microenvironment (TME) by maintaining the pH through aerobic glycolysis. Methods: We explored the expression of CD47 and MCT1 in breast invasive ductal carcinoma specimens to determine their association with prognosis. A total of 137 breast invasive ductal carcinoma tissues were collected for CD47 and MCT1 immunohistochemical staining. Results: Statistically analyzed, our study first indicated that in both univariate and multivariate analyses, the coexpression of CD47 and MCT1 was an independent prognostic factor for a poor 10-year overall survival rate (10-OS) and 10-year progression-free survival rate (10-DFS) (P<0.05). In addition, the combined high expression of these two markers also led to worse OS and PFS rates in the TNM (II + III), histologic grade (I + II), HER2 overexpression and basal-like subgroups. High expression of CD47 and MCT1 and combined high expression of CD47 and MCT1 were associated with clinicopathological parameters, such as histological grade, TNM stage, death status, and recurrence status in breast cancer patients. However, in the multivariate survival analysis, high expression of CD47 alone was not an independent prognostic factor for the 10-OS or the 10-DFS (P=0.104; P=0.153), and high expression of MCT1 alone was not an independent predictor for a poor 10-DFS (P=0.177) either. Conclusions: The coexpression of CD47 and MCT1 can serve as a prognostic biomarker leading to poor survival and an increased risk for recurrence, and this novel information could help guide the development of adjuvant therapy for breast cancer.