Background: 5% of screening mammograms demonstrate intramammary lymph nodes (IMLN). Prior to breast-conserving therapy (BCT), patients with breast cancer underwent total mastectomy, which removed IMLN whether they contained metastatic foci or not; since BCT, patients underwent partial mastectomy, which may or may not have removed these nodes. The authors do not support this approach and excise all ipsilateral IMLNs in patients with breast cancer. This study exams the oncologic merits of this practice. Methods: Since 2007, the authors have kept prospective data on all patients with IMLNs. 18 patients were identified who: 1) were diagnosed with ductal carcinoma, 2) had IMLNs detected pre-or intra-operatively, 3) underwent surgery. Data on age, history, physical exam, workup, treatment, pathology, and follow-up were reviewed. Results: All patients were female. The median age was 54 (36-92). Median 5-year and lifetime risks of developing breast cancer were: 1.6% (0.4 — 2.8) and 11.4% (2.8 — 20.1) respectively. Compared to the general population, these represented increases in 5-year and lifetime risks of 0.1 % (-1.4 — 1.4) and 1.0% (-4.7 — 8.2) respectively. 1 patient carried a mutation in BRCA1. 53% presented with a palpable mass; 47% presented with a lesion on screening mammography. Tumors and IMLNs were located in all four quadrants. In 5 patients (28%), the primary tumor and IMLN were located within different quadrants. Despite this spatial separation, in 3 of these patients, IMLNs contained metastatic foci; moreover, in 2 of these patients, the IMLN was the only positive node. 56% of all patients were initially treated with lumpectomy. Of these, 20% ultimately underwent mastectomy. Thus, 44% of all patients were treated with BCT. The median primary tumor size was 2.2 cm (0.3 — 7.8). 89% of tumors were both ER/PR-positive; 11 % were both ER/PR-negative. In 1 patient (6%), the tumor was positive for Her2/Neu overexpression. 78% of all patients underwent sentinel-node biopsy. For each, a median of 2 sentinel nodes (1 - 5) were retrieved. In 4 of these patients (29%), the sentinel node was intramammary. Moreover, among all patients with positive nodes, in a third (4 of 12), the IMLN was the only positive node. Indeed, in 42% of patients, IMLNs were directly responsible for upstaging disease. 44% of all patients and 64% of BCT patients underwent adjuvant radiation therapy. 56% of all patients underwent adjuvant chemotherapy; 56%, adjuvant hormonal therapy. At a median follow-up of 18 months (1-38), 94% remained disease free; 1 patient (6%) developed bony disease. Conclusions: This small prospective analysis sought to answer the following: 1) can IMLNs be excised in the setting of BCT1 and 2) should IMLNs be excised? For 72% of all patients, the primary tumor and IMLN were located within the same quadrant. Therefore, excision of the former readily incorporated the latter. For other patients, numerous techniques — ultrasonography, pre-operative wire placement, or palpation through the surgical wound — facilitated localization and removal. The oncologic merits of IMLN excision are clear — in 29% of patients undergoing sentinel lymph-node biopsy, the IMLN was sentinel; in 42% of patients with positive lymph nodes, the IMLN was directly responsible for upstaging disease. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-19.