A 61-year-old female with past medical history of maculopapular rash reaction to ciprofloxacin and amoxicillin being treated for diverticulitis develops the same rash with administration of piperacillin/tazobactam and aztreonam. A diffuse maculopapular rash developed after the administration of piperacillin. It resolved with discontinuation of the drug and the patient was switched to aztreonam and a very similar rash developed subsequently. In a review of the literature, there are no documented cases of a patient with an allergy to both aztreonam and piperacillin/tazobactam despite in vivo cross-reactivity. Unfortunately, there are no standardized allergy tests for aztreonam or piperacillin. This case, however, does offer the possibility that aztreonam may not always be the right alternative to persons with beta-lactam antibiotic allergies.