The significance of positive cytokeratin immunohistochemical(lHC) staining in sentinel axillary lymph nodes in breast cancer remains unclear. Authors reviewed a database of 904 consecutive patients participating in a sentinel lymph node(SLN) biopsy study at UTSW. There were 58 out of 904 patients (6.4%) who lacked evidence of SLN metastasis by hematoxylin-eosin stain but were found to have IHC positive cells in the SLN. Forty-seven of the 58 patients subsequently underwent axillary lymph node dissection (ALND). The characteristics of these 47 patients included a median age of 55 (37-76) and a median primary tumor size of 2.0 (0.4-7.2) cm. The location of the primary tumor included 25(53%) upper outer quadrant, 7(15%) upper inner quadrant, (11%) lower inner quadrant, 3(6%) lower outer quadrant, and 7(15%) between quadrants. Thirty-four (72%) of the patients had positive estrogen receptors (ER). Her-2-neu positive tumors were found in 12 (26%) of the patients. The median number of lymph nodes removed was 3 (1-7) for SLN biopsy and 17 (4-31) for ALND. There were two (4%) patients who had additional positive nodes found at ALND. One of the patients with a primary tumor size of 2.3 cm invasive ductal histology(IDC), ER ( + ), and Her-2-neu (-) had 1 mm metastasis in a SLN, but had 13 of 16 lymph nodes with metastasis on ALND. The other patient with a primär)- tumor size of 3.9 cm IDC, ER (-), and Her-2-neu (-) had three SLNs each with 1 mm metastasis and 2 of 9 lymph nodes with metastasis on ALND each containing 0.4 cm metastasis. In conclusion, the patients with only 1HC slain evidence of SLN metastasis have a low likelihood of additional metastasis at ALND. However, those patients who did have additional métastases had significant disease burden that would likely manifest as a clinical problem without ALND. Additional studies are required to better define parameters that predict for additional positive nodes at ALND.