Though exposure to radiation can cause acute, near-immediate effect by killing cells and directly damaging tissue, radiation can also have effects that happen on longer scale, such as cancer, by causing mutations in the DNA of living cells. Mutations can occur spontaneously, but a mutagen like radiation increases the likelihood of a mutation taking place. In theory, ionizing radiation can deposit molecular-bond-breaking energy, which can damage DNA, thus altering genes. In response, a cell will either repair the gene, die, or retain the mutation. In order for a mutation to cause cancer, it is believed that a series of mutations must accumulate in a given cell and its progeny. For this reason, it may be many years after exposure before an increase in the incident rate of cancer due to radiation becomes evident.

Among the long-term effects suffered by atomic bomb survivors, the most deadly was leukemia. An increase in leukemia appeared about two years after the attacks and peaked around four to six years later. Children represent the population that was affected most severely. Attributable risk—the percent difference in the incidence rate of a condition between an exposed population and a comparable unexposed one — reveals how great of an effect radiation had on leukemia incidence. The Radiation Effects Research Foundation estimates the attributable risk of leukemia to be 46% for bomb victims.