Introduction Hypersensitivity reactions from intravenous (IV) etoposide have been rarely reported, with these being seen more commonly with etoposide than with etoposide phosphate. This is generally explained by the need for polysorbate 80, a known cause of hypersensitivity, as a solubiliser, in the etoposide formulation. Case report We report a 22-year-old male, being treated with adjuvant BEP (bleomycin/etoposide phosphate/cisplatin) for a testicular germ cell tumour. Bleomycin and cisplatin were administered without incident. Within one minute of etoposide phosphate commencement he experienced a severe hypersensitivity reaction, consisting of widespread erythematous rash, facial swelling, and nausea. Observations included unrecordable blood pressure, tachycardia, hypoxia, and loss of consciousness, confirming a diagnosis of anaphylactic shock. Management and outcome Etoposide phosphate was ceased immediately. He was successfully managed with IV hydrocortisone, IV promethazine, intramuscular adrenaline, IV fluids and oxygen. Following admission for observation, significant improvement occurred over 48 h. Discussion Hypersensitivity reactions to etoposide were first reported in the 1980s. Following reactions to etoposide, substituting etoposide phosphate into chemotherapy regimens has commonly allowed treatment to continue without incidence. Anaphylactic reactions to etoposide phosphate were first documented in 2012, with further cases reported subsequently. Unlike etoposide, etoposide phosphate is highly soluble in aqueous solutions and doesn't require adjuvants in the formulation. Hypersensitivity reactions to etoposide phosphate are therefore likely related to the etoposide drug molecule itself. Clinicians should be aware of this rare, but potentially life-threatening, toxicity when using etoposide-based treatments and have procedures in place to urgently manage any hypersensitivity reactions that may occur.