<b><i>Background and Objective:</i></b> The aim of this study was to investigate the value of programmed death ligand 1 (PD-L1) expression as a predictive biomarker for Miller/Payne grading before neoadjuvant chemotherapy (NACT) in breast cancer. <b><i>Patients and Methods:</i></b> The expression of PD-L1 in pretreatment biopsies of breast cancer was assessed by immunohistochemistry in tissue microarrays. The results were analyzed using SPSS 22.0 statistical software. <b><i>Results:</i></b> Of 53 female patients, 10 (18.9%) patients had a grade 5 (G5) response, and 12 (22.6%) patients showed PD-L1 expression, including 7 (13.2%) patients with staining in tumor cells (TCs) and 8 (15.1%) patients with staining in peritumoral lymphocytes (PTLCs). Logistic regression analysis revealed that G5 response to NACT was significantly associated with TCs or PTLCs PD-L1 positivity, whether with univariate analysis (TCs PD-L1: <i>p</i> = 0.00, OR 20.50, 95% CI 3.11–134.94; PTLCs PD-L1: <i>p</i> = 0.02, OR 6.50, 95% CI 1.27–33.20) or with multivariate analysis (TCs PD-L1: <i>p</i> = 0.00, OR 42.23, 95% CI 3.36–530.90; PTLCs PD-L1: <i>p</i> = 0.02, OR 9.07, 95% CI 1.37–60.02). The same trend was found in the luminal subgroup analysis (TCs PD-L1: <i>p</i> = 0.02, OR 23.43, 95% CI 1.66–331.58; PTLCs PD-L1: <i>p</i> = 0.01, OR 47.89, 95% CI 2.47–927.41). <b><i>Conclusion:</i></b> G5 response to NACT in breast cancer was significantly associated with TCs or PTLCs PD-L1-positive expression in pretreatment biopsies; it can be expected that PD-L1 will become a new independent biomarker of response to NACT in breast cancer.