No familial marker chromosome associated with a malignancy has been reported to date. We used fluorescence in situ hybridization (FISH) to characterize a supernumerary marker chromosome 15 ascertained during prenatal diagnosis. This supernumerary chromosome 15 was found to span three generations of a family. Three family members carrying the supernumerary chromosome 15 have also had malignancies, namely, a cystic glioma, leukemia, and thyroid cancer.