With the advent of the CRISPR/Cas9 system, genome editing in various fields is advancing. Unintended mutation in off-target regions is a major problem of genome editing using the CRISPR/Cas9 system, and it is being reviewed. However, we found a high frequency and various unintended mutations in the “on-target” region when we generated a “knock-in” mouse with point mutation using this technique to develop a supernumerary rib model. Additionally, an inserted sequence of unknown origin was observed. Furthermore, these mutations were transferred to the next generation, even if tandem knock-in or large deletions occurred. These strongly suggest that a proper selection that meets the purpose is essential when considering the safety of foods and medicines using the genome-editing technology.