The sentinel node hypothesis is predicated on the fact that a metastasis, if it exists, will have traveled on a direct path from the primary tumor through the efferent lymphatic channels to the first draining lymph node in the regional lymphatic basin, the sentinel node. Lymphatic mapping with isosulfan blue and sentinel lymphadenectomy is being increasingly used in the management of patients with melanoma, breast cancer, and other solid tumors. This trend is exposing an increasing number of patients to isosulfan blue. Although this compound is generally safe, severe reactions have been reported. We describe 2 patients who developed "blue hives" after isosulfan blue injection.