In a diploid fibroblast culture from a patient with Fanconi anemia (FA), we observed the evolution of a chromosomally abnormal clone that had an unusual proliferative advantage and increased growth potential compared with the diploid FA cells. Q-, G-, C-, and Ag-NOR banding analyses revealed that the clonal cells had the chromosomal complement 46, XY, –5,-21, + marl,+mar2, and were trisomic for a segment of the long arm of chromosome 5 and most of the long arm of No. 21. The retention of chromosome instability in the clonal cells indicates that the alteration in growth characteristics did not result from a mutation to the wild-type allele at the FA locus.