Here we evaluated the cytotoxic effects of a combination of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and taxanes in human breast cancer cell lines. Combination treatment with taxane and SAHA had a synergistic cytotoxic effect against taxane-resistant breast cancer cells. Oligonucleotide microarray analysis identified 28 genes (MAPK13, ATP2C1, ANKRD57, MT1G, RGL4, C12orf49, EXOC6, RAB4A, TM9SF3, IFNGR1, DMD, HCG9, KIFC3, SYNGR3, NDRG4, NT5E, EOMES, SMC4, LANCL1, SCHIP1, and 8 ESTs) whose expression correlated with the combined effect of paclitaxel and SAHA. Twelve of these genes were down-regulated in cell lines that were paclitaxel-resistant but combination synergistic. SAHA induced NT5E mRNA expression in paclitaxel-resistant YCC-B1 cell. Our results indicate that a combination of taxane and SAHA could be efficacious for the treatment of breast cancer and that genes involved in the synergistic response to paclitaxel and SAHA could serve as biomarkers to predict therapeutic response in breast cancer patients.