Purpose To evaluate the potential of Tc-99m diphosphonate as a tracer for sentinel lymph node biopsy in breast cancer. Methods Lymphoscintigraphs of 35 patients ($50.9{pm}10.2$ years) with breast cancer were acquired after administering a subareolar intradermal injection of Tc-99m diphosphonate 18 h before surgery. Static images were taken within 15 min (early phase) and 15 h after injection (delayed phase). The lymphoscintigraphic identification rate was defined as the percentage of subjects studied with visible foci at axillae. Sentinel lymph node biopsies were performed using a gamma probe and by blue dye injection. Any node that was radioactive or stained with blue dye was labeled as a sentinel lymph node. Lymph nodes without radioactivity or blue dye staining were defined as nonsentinel lymph nodes. The intraoperative identification rate was defined as the percentage of patients with a radioactive sentinel lymph node. Percentages of lymphoid cells expressing S-100, CD83, and CD1a were compared. Results The lymphoscintigraphic identification rate was 94.3% (33/35) during the early phase and 96.9% (31/32) during the delayed phase, whereas the intraoperative identification rate was 94.3% (33/35). The mean percentages of lymphoid cells that stained positively for S-100 or CD83 were lower in sentinel lymph nodes than in nonsentinel lymph nodes (1.5% vs. 9.0% for S-100, and 4.5% vs. 9.3% for CD83, respectively, p=0.0286). The mean percentages of lymphoid cells in sentinel lymph nodes and non- sentinel lymph nodes expressing CD1a were 3.3% and 7.0%, respectively (p=ns). Conclusions Tc-99m diphosphonate can reliably detect regional lymph nodes in breast cancer.