Venous flare reaction, a localized allergic response associated with the administration of an irritant, is one of the most common chemotherapy infusion-related reactions. Etoposide, a drug commonly used in patients with lung cancer, has been reported to be an irritant with vesicant properties depending on the volume administered. This article presents the case of a patient who has a venous flare reaction immediately following the administration of etoposide for the treatment of diffuse large B-cell lymphoma. Managing such complications is crucial to maintaining patient safety. Proper training and education should be incorporated into nursing practice when identifying, preventing, and managing such reactions.