This study evaluated the association between family history of cancer and bleomycin-induced mutagen breaks at specific chromosomes. The authors' hypothesis was that individuals exhibiting mutagen-induced specific chromatid breaks might have genetic instability and thus be more likely to report a family history of cancer. The study included 78 healthy individuals. All subjects completed a personal interview to collect epidemiologic information, including a detailed family history of cancer, and donated a 10-mL blood sample. Bleomycin-induced mutagen sensitivity on specific chromosomes was quantified by counting the bleomycin-induced specific chromosomal breaks with Q-banding techniques. We found that chromosome 4 breaks were significantly associated with a positive family history of cancer in first-degree relatives with an odds ratio of 3.18 and 95% confidence interval of 1.05-9.61. However, none of the other chromosomes showed significantly increased risk with family cancer history. In addition, the mutagen-induced chromosome 4 breaks were not associated with age, sex, ethnicity, or smoking status. These findings suggested that chromosome 4 mutagen sensitivity might be a predictor of familial susceptibility to cancer.