Chromosomal variability was studied in cultured skin fibroblasts in members of two unrelated families associated with hereditary neoplasms, one with familial childhood leukemia and the other with medullary thyroid cancer syndrome. Nonconstitutional chromosome rearrangements occurred with consistent frequency in the patients and obligate carriers. The G-banding analysis showed that th chromosome rearrangements were not random, and site of rearrangements tended to cluster to band p22 of chromosome 1 in the carriers of childhood leukemia gene and to band q23 of chromosome 17 in the patient with medullary thyroid cancer. The de novo rearrangements of chromosomes and their tendency to cluster to particular chromosomal sites strongly point to the possibility that the procancer type-dominant mutations responsible for these diseases have a mutator function analogous to the property of some insertion mutations or transposable elements.