Background <p>Frozen section evaluation can be used for intraoperative diagnosis of sentinel lymph node (SLN) metastases. When completion axillary lymph node dissection is planned owing to positive SLNs following neoadjuvant chemotherapy (NACT), frozen section may be considered to facilitate completion of axillary surgery at the index operation. The utility of intraoperative SLN assessment with frozen section in patients with hormone receptor-positive (HR⁺) breast cancer depends on the prevalence of SLN positivity and frozen section accuracy.</p> Patients and Methods <p>We conducted a single-institution observational cohort study including patients with noninflammatory, cN0, HR⁺, defined as either estrogen receptor-positive (ER⁺) and/or progesterone receptor-positive (PR⁺), HER2-negative breast cancer treated with NACT between 2015 and 2021. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section.</p> Results <p>Of 145 eligible patients, 47 (32.4%; 95% confidence interval [CI]: 24.9, 40.7) had SLN metastases. Positive SLNs were more frequent among those with ER⁺ PR⁺ tumors compared with ER⁺ PR⁻ or ER⁻ PR⁺ tumors, larger clinical T category, and invasive lobular histology. Among 115 patients with SLNs assessed by frozen section, the true prevalence of metastases was 31.3% (95% CI: 23.0, 40.6), while frozen section identified only 17.4% (95% CI: 11.0, 25.6) as positive. Frozen section sensitivity was 55.6% (95% CI: 38.1, 72.1), and specificity was 100% (95% CI: 95.4, 100.0). Sensitivity for micrometastases or isolated tumor cells was limited (23.5%; 95% CI: 6.8, 50.0).</p> Conclusions <p>In patients with cN0 HR⁺, HER2-negative breast cancer, SLN positivity after NACT varies and is more common in high-risk subgroups of this population. Frozen section has modest sensitivity overall and is more limited for the diagnosis of low-volume nodal disease. Use of frozen section may be warranted where avoiding reoperation is a priority.</p>