A significantly increased incidence of heterochromatic chromosomal variants, particularly of Ai and Cy, has been found in a group of 120 patients with malignant or premalignant diseases. People presenting with such a kind of polymorphism usually have an increased chromosomal breakage rate. Genetically increased susceptibility to breaking agents may be the unifying concept explaining the increased incidence of heterochromatic variants found in couples with sterility or abortions, in karyotypically normal malformed or retarded children, and in patients suffering from different malignant or premalignant diseases. Chromosomal imbalance is probably the basis for initiation of malignancy whose development is influenced by many different factors.