Tc-99m sestamibi (MIBI) is a relatively noninvasive diagnostic modality in the evaluation of breast cancer. The purpose of this study was to review the existing literature on the accuracy of Tc-99m MIBI in the diagnosis of breast cancer. After a systematic review of English-language studies, the sensitivity, specificity, and other measures of accuracy of Tc-99m MIBI in the diagnosis of breast cancer were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize the overall test performance. Forty-five studies met our inclusion criteria. The summary estimates for Tc-99m MIBI in the diagnosis of breast cancer in the studies included were as follows: sensitivity, 0.83 [95% confidence interval (CI), 0.82-0.84]; specificity, 0.85 (95% CI, 0.83-0.86); positive likelihood ratio, 5.06 (95% CI, 4.26-6.01); negative likelihood ratio, 0.20 (95% CI, 0.17-0.24); and diagnostic odds ratio, 27.63 (95% CI, 21.63-36.10). For patients with a palpable mass, the sensitivity and specificity were 87 and 86%, respectively. For patients without a palpable mass, the sensitivity and specificity were 59 and 89%, respectively. Tc-99m MIBI has a high level of overall accuracy for the diagnosis of breast cancer.