Phyllodes tumors are not quite rare fibroepithelial neoplasms of the breast that show a broad spectrum of clinical behaviour. The molecular genetic features of the heterogenous groups of neoplasms have not been studied in detail yet. We have used comparative genomic hybridization to analyze chromosomal copy number changes in 36 cases of phyllodes tumors (including benign, borderline and malignant phyllodes tumors, 12 cases each). The average number of chromosome copy changes (range) in benign, borderline and malignant phyllodes tumors were 5.58 (0-20), 14.08 (3-23), and 12.42 (0-29) respectively. In benign phyllodes tumors the number of gains and losses was in balance (2.50 vs 3.08), while in borderline and malignant phyllodes tumors gains occurred more often than losses (9.25 vs 4.83, 9.5 vs 2.92). The result suggests the molecular cytogenetics of borderline and malignant phyllodes tumors is similar, and the most striking difference with benign phyllodes tumors is an increased number of chromosomal gains in a nonrandom distribution. Gains of 4q12 seem especially to be involved in the progression of benign to borderline and malignant phyllodes tumors, possibly because of overexpression of oncogenes at these loci.