The status of the regional nodal basin remains the most important prognostic indicator of survival. The current standard of care for the management of invasive breast cancer is the complete removal of the tumor, with documentation of negative margins by either mastectomy or lumpectomy, followed by complete axillary lymph node dissection. Data suggest that complete lymph node dissection (CLND) provides better local control of the disease and may actually offer a survival advantage. Lymphatic mapping and sentinel lymph node (SLN) biopsy are clearly changing this long-held paradigm and have the potential to change the standard of surgical care of the breast cancer patient. The purpose of this report is to describe the lymphatic mapping experience at the H. Lee Moffitt Cancer Center and Research Institute. From April 1994 to January 1999, 1,147 consecutive breast cancer patients were enrolled in an institutional review board-approved lymphatic mapping protocol. Lymphatic mapping was performed using Tc99m-labeled sulfur colloid and isosulfan blue dye. An SLN was defined as any blue node and/or any hot node with ex vivo radioactivity counts >/=10 times an excised non-SLN or in situ radioactivity counts >/=3 times the background counts. Lymphatic mapping was successful in identifying the SLN in 1,098 of 1,147 (95.7%) cases. In the first 186 patients, all of whom underwent CLND following SLN biopsy, one false-negative biopsy was encountered for a false-negative rate of 0.83%. The method of diagnosis (excisional versus minimally invasive) does not appear to impact on lymphatic mapping. Tumor size, however, is directly related to the probability of axillary lymph node involvement. Advances in technology and the development of minimally invasive surgical techniques have heralded a new era in surgery. Lymphatic mapping and SLN biopsy may actually prove to be a more accurate method of identifying metastases to the axilla by allowing a more focused pathologic examination of the axillary node(s) at highest risk for metastasis. With adequate training, this technique can be readily implemented as a valuable tool in the surgical treatment of breast cancer.