Presented is an interesting case of a patient with diagnosis of central nervous system (CNS) malignancy and Hashimoto thyroiditis, who developed anaphylaxis to low sorb tubing which was used for chemotherapy and supportive care medication. The patient had no known drug allergies and an unremarkable work up for hereditary angioedema, rheumatological and immunodeficiency disorders. This hypersensitivity reaction (HSR) has not been previously reported in literature and delayed the patient’s cancer related treatment, which has the potential of impacting patient outcomes. We report this rare case, discuss differential diagnosis for HSR in patients with negative allergy history, and provide management guidelines.