BACKGROUND: Lymphazurin 1% blue dye can cause a severe anaphylactic reaction in approximately 1-3% of patients. CASE PRESENTATION: We describe a case of intraoperative anaphylaxis resulting from Lymphazurin 1% blue dye. A 48-year old woman undergoing a mastectomy with sentinel lymph node biopsy experienced a biphasic anaphylactic reaction with two episodes of hypotension at 15 minutes and 2 hours, respectively, after injection of the blue dye. The late phase was initially refractory to epinephrine. CONCLUSION: Early recognition, aggressive hemodynamic management, and prolonged monitoring are indicated in these patients to watch for a potential second phase anaphylactic reaction.