Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified the collagen β(1-O) galactosyltransferase 2, COLGALT2, as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of COLGALT2 messenger RNA than did patients not treated with trastuzumab, demonstrating increased expression of an enzyme involved in collagen glycosylation and associated with metastasis and proliferation in osteosarcoma (5) as a transcriptional consequence of treatment with trastuzumab.