We have developed differential gene expression data sets from breast tumors through analysis of 8 in situ and 32 invasive breast tumors relative to 6 samples of normal breast tissue using arrays containing 40,000 DNA elements. Depending on the cutoff values used, 10–20% of these sequences are differentially expressed in breast tumors compared with normal breast tissues. We have taken the new approach of using centrosome amplification, a tumor-associated phenomenon, to rank tumors so that genes associated with this phenomenon can be identified for further study. Centrosome amplification has recently been identified as a feature common to many human tumors, including those of the breast. Proper structure and function of duplicated mitotic centrosomes are required for fidelity in chromosome segregation and preservation of diploidy. We have shown that in breast tumors centrosome amplification correlates with aneuploidy. In the present work, the degree of centrosome amplification was quantified by immunofluorescence microscopy. We ranked tumors by their degree of centrosome amplification, and genes whose expression strongly correlated with this ranking were identified. We are testing the biological significance of genes identified in this manner in a cell culture assay system designed to measure the effects of their overexpression on the structural and functional integrity of the centrosome and mitotic spindle apparatus. Given the obligate requirement for proper structure and function of mitotic and interphase centrosomes in regulation of mitosis and cell polarity, the identified subset of genes associated with centrosome amplification is probably involved in the cell cycle and the development of aneuploidy, both of which are key factors in cancer development and progression.