More detailed examination of the sentinel lymph node (SLN) in breast cancer has raised concerns about the clinical significance of micrometastases, specifically isolated tumor cells detected only through immunohistochemical (IHC) staining. It has been suggested that these cells do not carry the same biologic implications as true metastatic foci and may represent artifact. A retrospective institutional review board-approved review was conducted on clinically node-negative breast cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003. Retrospective analysis of tumor characteristics and the method of the initial diagnostic biopsy were correlated with the presence and nature of metastatic disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E) positive. SLN positivity strongly correlated with tumor size (p<0.001) and tumor grade (p=0.025), but not with the method of biopsy (needle versus excisional biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC (n=381). Of the 291 H&E-negative patients, 26 had IHC-only detected micrometastases (9%). The likelihood of detecting IHC-only metastases did not correlate with tumor size or grade, but was significantly higher in patients undergoing excisional biopsy than core needle biopsy. While the method of biopsy has no demonstrable effect on the likelihood of finding metastases in the SLN by routine serial sectioning and H&E staining, it may significantly impact the likelihood of finding micrometastases by IHC. IHC should not be used routinely in the evaluation of the SLN and caution should be used when basing treatment decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC-only detected micrometastases.