Breast cancer (BC) is the most common malignancy in women. The aim was to assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST), both at surgery and during the 4-year postoperative period. Patients and methods: We retrospectively included 375 women with an early clinical stage of non-luminal A IDC-NST who between 2007 and 2013 underwent breast surgery at the Clinical Hospital Center Rijeka. They were divided into 4 phenotype-based groups: HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. Radiotherapy was delivered in patients who underwent breast-conserving surgery, as well as in those with mastectomy if >3 ALNs were positive. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumour size, higher grade, HR+, HER2+ status, and lymphovascular invasion were predictive for ALN involvement at surgery. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were observed in the HR-/HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was found in HR-/HER2+ and HR-/HER2- groups. Histologic grade, HR status, lymph node ratio, lymphovascular invasion, and tumour size were significant predictors of OS, DFS, LRFS, and DRFS, while HER2 status was not. Conclusion: Despite the predictive capacity of HER2+ status for ALN involvement at diagnosis, HER2 status had no effect on 4-year OS, DFS, LRFS and DRFS in IDC-NST patients who received phenotype-based postoperative systemic treatment according to the St. Gallen Conference recommendations. The results indicate the beneficial effects of HER2-targeted therapy in HER2+ IDC-NST.