Using comparative genomic hybridization (CGH), array CGH, fluorescence in situ hybridization, and loss of heterozygosity analysis, we examined a recurrent solitary fibrous tumor of the orbit for chromosomal imbalances. In the primary tumor, loss of chromosomal material was observed at 9p, 9q, and 16q. In the first recurrent tumor, cells with these abnormalities were detected, but in some parts of the tumor, cells with losses at 13q (homozygous deletion at 13qter) and 20p were dominant. In the second recurrence, only cells with losses at 13q and 20p were seen. Although morphologically similar, the second recurrent tumor invaded the anterior cranial fossa and demonstrated considerably faster growth than the first recurrent tumor. Thus, the clone of tumor cells that dominated the second recurrent tumor was shown by cytogenetic analysis to be different from that present in the primary tumor, and was associated with a more aggressive nature of the tumor.