In vitro detection of micronuclei was used to determine spontaneous chromosomal instability in cultured fibroblasts of 28 healthy normal controls, 28 individuals with nonfamilial cutaneous malignant melanoma (CMM) and 14 people with familial occurrence of CMM. Lymphocytes from 40 healthy controls, 40 CMM patients and 6 individuals with familial CMM were also compared for spontaneous expression of micronuclei in vitro. In the familial cases micronucleus frequency was found to be higher, both in cultured fibroblasts (P less than 0.005) and in lymphocytes (P less than 0.001) as compared to normal controls. There was no significant difference between nonfamilial cases and normal controls. We conclude that chromosomal instability may contribute to a genetic risk for development of cutaneous malignant melanoma.