We have recently described a higher incidence of multiple primary cancers in A-bomb survivors. Inasmuch as a long-lasting radiation effect is considered to be a contributing factor in tumorigenesis in the survivors, the molecular mechanisms involved are not yet understood. The incidence of basal cell carcinoma (BCC) of skin was reported to be elevated in the survivors, suggesting a radiation etiology in skin carcinogenesis as well as ultraviolet. Any DNA damages can induce DNA damage response (DDR) leading to genomic instability (GIN), which allows the accumulation of genetic mutations that is implicated in both initiation and progression of cancers. This study evaluated the presence of GIN in the epidermis surrounding BCC from the survivors. A total of 146 BCC were identified in the survivors from 1968 to 1999. Among 146 BCC, 23 cases arose at nonexposed skin consisting of 9 proximal, 4 intermediate, and 10 distal distance groups. Total 19 epidermis surrounding BCC at the nonexposed sites from 7 proximal, 5 distal, and 7 control groups were tested for 53BP1 expression with immunofluorescence to analyze the level of GIN. Because one manifestation of GIN is the induction of endogenous DDR, the level of 53BP1-focus formation (DDR type) can be considered as a marker for GIN. In results, the incidence rate of BCC increased significantly as exposure distance decreased from the hypocenter. Of the 7 epidermis in proximal group, five cases predominantly expressed DDR and abnormal type. In contrast, 4 of 5 cases in distal group and all cases in control groups predominantly expressed stable type in the epidermis. This study demonstrated the sporadic activation of DDR in the epidermis surrounding BCC from the survivors of proximal group, suggesting the presence of a GIN in the survivors as a late effect of A-bomb radiation which can be a cause of cancer predisposition.