Internal mammary lymphadenopathy (IML) plays a role in breast cancer stage and prognosis. We aimed to evaluate method of IML detection, how IML impacts response to neoadjuvant chemotherapy (NAC), and oncologic outcomes. We evaluated patients enrolled in the I-SPY-2 clinical trial from 2010 to 2022. We captured the radiographic method of IML detection (magnetic resonance imaging [MRI], positron emission tomography/computed tomography [PET/CT], or both) and compared patients with IML with those without. Rates of locoregional recurrence (LRR), distant recurrence (DR) and event-free survival (EFS) were compared by bivariate analysis. Of 2095 patients, 198 (9.5%) had IML reported on pretreatment imaging. The method of IML detection was 154 (77.8%) MRI only, 11 (5.6%) PET/CT only, and 33 (16.7%) both. Factors associated with IML were younger age (p=0.001), larger tumors (p<0.001), and higher tumor grade (p=0.027). Pathologic complete response (pCR) was slightly higher in the IML group (41.4% vs. 34.0%; p=0.03). There was no difference in breast or axillary surgery (p=0.41 and p=0.16), however IML patients were more likely to undergo radiation (68.2% vs. 54.1%; p<0.001). With a median follow up of 3.72 years (range 0.4-10.2), there was no difference between IM+ versus IM- in LRR (5.6% vs. 3.8%; p=0.25), DR (9.1% vs. 7.9%; p=0.58), or EFS (61.6% vs. 57.2%; p=0.48). This was true for patients with and without pCR. In this large cohort of patients treated with NAC, outcomes were not negatively impacted by IML. We demonstrated that IML influences treatment selection but is not a poor prognostic indicator when treated with modern NAC and multidisciplinary disease management.