In the United States, identification of the sentinel lymph node (SLN) requires the use of 99mTc-labeled colloid, 1% isosulfan blue dye, or both to trace the lymphatic drainage of a given neoplasm. We report our experience with adverse reactions to isosulfan blue dye during SLN mapping in breast cancer. A chart review of the breast cancer SLN database was performed; it included 2392 sequential patients who underwent SLN biopsy involving isosulfan blue dye at Memorial Sloan-Kettering Cancer Center from September 12, 1996, to August 17, 2000. Thirty-nine of 2392 patients (1.6%) had a documented allergic reaction during the mapping procedure. Most reactions (69%) produced urticaria, blue hives, a generalized rash, or pruritus. The incidence of hypotensive reactions was 0.5%. Although anaphylaxis after the injection of isosulfan blue dye is rare, this article highlights the need to suspect anaphylaxis when hemodynamic instability occurs after the injection of this compound. Our experience indicates that bronchospasm and respiratory compromise are unusual and that most patients do not require emergent intubation and can be managed with short-term pressor support. In addition, our data indicate that patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye.