Background: Tumour infiltrating lymphocytes (TILs), have been associated in higher responses to treatment and are thought to be a prognostic marker in a number of cancer types. The role of TILs in breast cancer varies depending on the molecular subtype of the disease. In hormone positive, HER2-negative breast cancer, the significance of TILs is less clear, partly due to the paucity of data in this area. We aim to assess overall TILs in early-stage, hormone-positive, HER2-negative (ER+/HER2-) breast cancer and its relationship with proliferation index, Ki67, and the 21-gene recurrence score. Methods: Archival patient tissue samples of early-stage, ER+/HER2- breast cancer from the Irish arm of the TAILORx clinical trial were used. Full-face sections of these tumours were stained with anti-CD45 antibody (DAKA clone M0701) via the automated Leica Bond III system. A watershed cell-detection algorithm from the open-source digital pathology software, QuPath, was fine-tuned to identify true cell objects and positive immune markers. Optimised detection parameters were used to calculate the percentage of overall CD45+ cells (CD45%) within the tumour area. Patient TIL categories were dichotomised into High v Low CD45%, with 10% chosen as the threshold. CD45% was further correlated with proliferation index, clinical data, and 21-gene recurrence score. Results: 409 samples were included in the analysis. The mean CD45% was 5.96, with samples ranging from 0.13 to 78.86. The majority of samples were in the range of 0-10% of CD45% positivity with 89% (n = 367) patients in this category. Stratification of the cohort by 21-gene-recurrence score (RS) into Low, Intermediate and High, showed a statistically significantly high CD45% in patients with a High RS compared to Low RS (p = 0.0015). When divided by recurrence score group, high CD45% trended toward a lower disease free survival (DFS) when compared to low CD45%, with statistical significance found in those in the Intermediate RS chemotherapy treatment arm (p = 0.009). Conclusions: The role of TILs in ER+/HER2- breast cancer is still undefined. While a High RS was associated with a higher percentage of CD45-positive lymphocytes, the impact on recurrence and response to treatment remains unclear. Further studies to assess the role of different tumour infiltrating lymphocyte phenotypes, and the spatial distribution of assessed markers, are needed.