BACKGROUND: Breast cancer has significant biologic heterogeneity, which influences treatment decisions. We hypothesized that in postmenopausal women (≥ 50 years) with clinical T1-2, N0, hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer of special histology (mucinous, tubular, cribriform, papillary), information from sentinel lymph node biopsy (SLNB) may not change adjuvant therapy recommendations. PATIENTS AND METHODS: We constructed a cohort from the National Cancer Database of women aged ≥ 18 years with cT1-2 N0 HR+ HER2- invasive breast cancer. We calculated the frequency of nodal positivity by histology. We measured the frequency of N2/N3 disease, the distribution of Oncotype DX 21-gene assay recurrence score (ODX RS) across special histology by nodal status, and frequency of chemotherapy use by ODX RS and pathologic N stage. RESULTS: In women with cN0 HR+/HER2- special histologic subtype breast cancer, the likelihood of pathologic nodal positivity is less than 5%, and 99.7% of patients had N0 or N1 disease. Among women aged ≥ 50 years with HR+/HER2- special histologic subtype breast cancer, there was low prevalence of high ODX RS > 25 in both N0 and N1 patients (7% overall). Receipt of chemotherapy correlated with Oncotype DX scores as anticipated, with the lowest use in women with a low/intermediate RS (from 2 to 6% for N0 and 6-24% for N1) and the highest use in women with high risk Oncotype scores (from 74 to 92%). CONCLUSIONS: Our study suggests that SLNB could potentially be omitted in select postmenopausal women with cT1-2 N0 HR+/HER2- special histologic subtype breast cancer when ODX RS is available.