This article presents a case report of perioperative anaphylaxis in a previously nonallergic 44-year-old man undergoing cervical spine surgery. After receiving general anesthesia with midazolam, propofol, lidocaine, fentanyl, rocuronium, and sevoflurane and cefazolin for prophylaxis, the patient developed hypotension, tachycardia, bronchospasm, and generalized erythema. A serum tryptase concentration was markedly elevated 2 hours after the anaphylactic episode. Initial prick and intradermal skin tests (excluding skin testing for unavailable benzylpenicilloyl polylysine) and IgE immunoassays for penicillin and cefazolin were negative. However, repeat prick skin testing for cefazolin 6 weeks after anaphylaxis was positive. Although anaphylaxis to cephalosporins is rare, it remains a potential cause of perioperative anaphylaxis. All cases of perioperative anaphylaxis require a workup to identify the offending agent and to avoid future reactions. Skin testing regimens for several commonly implicated drugs used for general anesthesia are available and are described.