Cephalosporins were introduced into the U.S. market in 1964 and soon followed case reports of hypersensitivity reactions, some occurring in patients with a history of penicillin allergy. Cephalosporins share a similar beta-lactam chemical structure with penicillins, thus the concept of cross-reactivity was proposed. A meta-analysis of this issue, published in 1978, revealed 8.1% of patients with prior penicillin allergy subsequently develop cephalosporin allergy compared to only 1.9% without a prior penicillin allergy. This 8.1% cephalosporin allergy rate is the basis for the widely cited (and rounded up) 10% cross-reactivity rate that has become engrained in healthcare providers. However, major concerns such as lack of a definition of allergy and the fact that cephalosporins used during this time period were known to have been contaminated with penicillin during the manufacturing process raise doubt as to the validity of this data. This is highlighted by the fact that current studies do not support a clinically significant cross-reactivity between penicillin and cephalosporins.