Spontaneous chromosomal instability has been correlated with cancer predisposition. In the present study, the phenomenon has been evaluated using two cytogenetic markers, namely, frequency of spontaneous sister chromatid exchanges (SCE) and spontaneous chromosomal aberrations (CA) in peripheral blood lymphocytes of hereditary breast cancer (HBC) patients (n = 11) and healthy blood relatives (HBR, n = 36). A statistically significant difference was observed for both the endpoints between HBC patients and controls (P < 0.001), HBC patients and HBR (P < 0.001), as well as HBR and controls (P < 0.001). Thus, 63.64% of the HBC patients and 25% of HBR showed a mean CA/cell value higher than the highest mean CA/cell value of the controls (0.11 CA/cell). Similarly, 81.81% of the HBC patients and 61.11% of HBR showed a mean SCE/cell value higher than the highest mean SCE/cell value of the controls (9.60 SCE/cell). Chromosomal aberrations were more frequently observed in the B and E group of chromosomes in HBC patients and HBR. These findings primarily indicate the high level of chromosomal instability in breast cancer families, and might be one of the predisposing factors for high risk of cancer in HBR.