Trastuzumab is a targeted therapy for human EGF receptor-2 (HER2)-positive breast cancer. The effectiveness and cost-effectiveness of trastuzumab hinges not only on its clinical efficacy in responding patients, but on the ability to accurately identify appropriate therapeutic candidates. We sought to systematically review the cost-effectiveness of trastuzumab with a focus on the impact of the test(s) used for HER2 diagnosis. Our review included 17 economic evaluations or health technology assessments of trastuzumab therapy or HER2 testing. Trastuzumab was considered cost-effective in all early-stage disease studies, while one author concluded that trastuzumab was not cost-effective for metastatic disease. Only two papers considered the joint effects of test accuracy and sequencing with trastuzumab therapy. These demonstrated that trastuzumab cost-effectiveness is sensitive to HER2-test properties.