A hematopoietic stem cell transplant patient with a history of immediate drug hypersensitivity reaction to micafungin was considered for a caspofungin trial. A caspofungin intradermal skin test was performed. The result was positive, suggesting the presence of cross-reactivity and that the cyclic peptide nucleus chemical structure shared between echinocandins is the site of IgE recognition. It is recommended to avoid challenging patients with history of immediate hypersensitivity to one echinocandin with another.