Chromosomal aberration and micronucleus assays were used to investigate the extent of cytogenetic damage in peripheral blood lymphocytes from four patients in two unrelated families with hereditary megaduodenum. The frequencies of total chromosomal aberrations, which significantly correlated with those of micronuclei, were higher in the patients than in sex- and age-matched controls, with no overlapping between the two groups. The considerable chromosomal fragility in patients with hereditary megaduodenum may be a genotypic marker for preclinical diagnosis predictive of increased cancer risk.