Abstract Background To investigate the impact of hormone receptor (HR) on the clinicopathological characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods Using the Surveillance, Epidemiology, and End Results database, we enrolled patients diagnosed with HER2-positive breast cancer between 2010 and 2016, which were successively assessed for eligibility and categorized into HR + /HER2 + and HR-/HER2 + subgroups. Clinicopathological characteristics were undergone comparative analyses with the baseline distinctions calibrated by propensity score matching, while the survival outcomes were compared using Kaplan–Meier method with log-rank tests. Results A total of 46,803 HER2-positive breast cancer patients were identified, of which 32,919 individuals were HR + /HER2 + subtype and 13,884 individuals were HR-/HER2 + subtype, respectively. Comparatively, HR + /HER2 + breast cancer presented a lower histological grade, a smaller tumor size, a lower nodal involvement, and a lower rate of de novo stage IV disease. Substantial heterogeneity was detected in the metastatic patterns of organ-specific involvement between the two subgroups with initial metastasis. Overall, patients with HR + /HER2 + tumors had increasingly favorable prognosis in terms of overall survival and breast cancer-specific survival than patients with the HR−/HER2 + subtype. However, this kind of tendency exhibited disparities associated with HR-specific subtypes based on estrogen receptor (ER) and progesterone receptor (PgR) status, in which ER−/PgR + tended to present the worst prognosis. Conclusion This study revealed profound heterogeneity associated with HR status in the clinical outcomes of HER2-positive breast cancer regarding clinicopathological features, metastatic patterns, and prognosis. Prospective studies to optimize therapeutic strategies for HER2-positive subgroups are warranted.