Background: The expansion of the spectrum of HER2 breast cancer (BC) to include HER2-low status has had major impact in oncology. More than half of the BC patients (pts) are now categorized as HER2-low. With the recent approval of antibody-drug conjugates in HER2-low BC, HER2-low has emerged as a distinct targetable entity. BC pts who attain pCR after neoadjuvant chemotherapy (NAC) have a better prognosis. We analyzed the association of race with attainment of pCR among HER2-low and HER2-zero pts treated with NAC and with survival. Methods: We queried the National Cancer Database for stage I, II, III BC pts who received NAC from 2010 – 2019. The population was divided into two cohorts: HER2-low and HER2-zero. All associations were compared using Kruskal-Wallis, Pearson’s Chi-Squared, and Fisher’s Exact Tests. Multivariate cox regression models were generated for overall survival (OS) adjusted for age, race, stage, grade, body mass index, treatments, subtypes, insurance and comorbidities. Results: A total of 72,279 pts was included in the analysis (HER2-zero = 71,091, HER2-low = 1,188). There was higher hormone receptor (HR)-positivity in HER2-low vs. HER2-zero groups (69% vs 54%, p < 0.001). Higher percentage of pts had private insurance in the HER2- low group (60% vs 4%, p < 0.001). Race, age, clinical T and N-staging were distributed equally between both cohorts. Among all races, those with HER2-low status had lower pCR compared to HER2-zero, but this was not statistically significant. The rate of pCR was similar across racial groups in both HER2-low and HER2-zero groups, though was not statistically significant. In the HER2-zero group, Blacks had worse while Asians had better survival compared to Caucasians in overall (Blacks: hazard ratio (HR) 1.36, 95% CI = 1.3-1.4; Asians: HR 0.60, 95% CI = 0.57-0.74), HR-positive (Blacks: HR 1.4, 95% CI = 1.3-1.4; Asians: HR 0.60, 95% CI = 0.53-0.75) and HR-negative (Blacks: HR 1.2, 95% CI = 1.17-1.29; Asians: HR 0.69, 95% CI = 0.58-0.83) subtypes (all p < 0.001). However, this racial disparity in survival was not observed in the HER2-low group in the overall population (Blacks: HR 1.1, 95% CI = 0.7-1.5, p = 0.5; Asians: HR 0.38, 95% CI = 0.14-1.03, p = 0.06) or within subtypes. Interestingly, among Blacks, pts with HER2-zero disease had worse survival compared to HER2-low disease (5-yr OS: 73% vs 81%, p = 0.02, HR 1.4, 95% CI = 1.05-1.9, p = 0.02). This survival difference was not observed in any other races. Conclusions: Racial disparity in survival plays a role in the HER2-zero, not in HER2-low early-stage BC. Blacks who received NAC have decreased OS in the HER2-zero group, not in HER2-low group compared to other races. More studies are needed to confirm this finding and identify the mechanism underlying this disparity. Among Blacks, those with HER2-zero BC had worse survival compared to HER2-low. This highlights the need for personalized treatment options for Blacks for HER2-zero BC.