Objectives: To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC). Methods PD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients ( n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples ( n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off. Results In the post-operative, post-NAC samples ( n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar’s, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples ( p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status ( p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate ( p > 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples ( t = 0.581, p = 0.563 or Wilcoxon’s Signed Rank test; z = -0.625, p = 0.529). Conclusion Our findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.