As part of the regulatory safety assessment for transgenic crops, the DNA of the genetic insert and insert/flanking-region junctions are searched for random reading frames that could encode unsafe proteins. In addition, the endogenous flanking regions are examined to determine if the insert disrupts endogenous genes or regulatory elements. We discuss the likelihood of these events in the context of traditional breeding and in the context of the probability that cryptic reading frames might encode unsafe proteins. We conclude that there is a lack of theoretical and empirical evidence to suggest that these safety risks are significant or different compared with those of traditional crop breeding.