Introduction: Breast cancer is the most common malignancy affecting women. Cyclin D1 overexpression is one of the basic genetic alterations which implicated in its carcinogenesis. PD-L1 acts as a promising biomarker emerging in several tumor types. Aim: To evaluate the immunohistochemical (IHC) expression of cyclin D1 and PD-L1 in invasive ductal carcinoma of the breast of no special type (IDC-NST) in different molecular subtypes, and to analyze the correlation between their expression with stromal tumor-infiltrating lymphocytes (TILs) density and response to neoadjuvant chemotherapy (NAC). Materials and Methods: This prospective study was conducted in Faculty of Medicine, Zagazig University, Egypt. A total of 80 patients diagnosed with IDC-NST were studied from January 2017 to May 2019. Specimens taken were 30 core biopsies before receiving NAC protocol, and 50 mastectomy specimens not received NAC. Data was statistically analyzed using SPSS 22.0 software. Results: PD-L1 expression was detected in 30.1% in tumor cells and in 22.5 % in TILs. There was a significant association between PD- L1 expression and stromal TILs (p<0.001).TILs density was high in 47.5 % of the cases mainly in triple-negative breast cancer. Cyclin D1 expression was observed in 56.3%. There was a significant association between PD-L1 expression and TNBC, and a significant association between luminal breast cancer and cyclin D1 expression. PD-L1 and cyclin D1 expression was significantly correlated with response to NAC. Conclusion: Cyclin D1 and PD-L1 may act as predictive biomarkers for response to neoadjuvant chemotherapy and can be targeted in future therapeutic approaches.