Epigenetic profiling to classify cancer types upon the microarray DNA methylation signatures with a reported specificity of 99.6% (95% CI 99.5–99.7), sensitivity of 97.7% (96.1–99.2), positive predictive value of 88.6% (85.8–91.3), and negative predictive value of 99.9% (99.9–100.0) in the validation set of 7691 known tumor samples. Methylation profiling also predicted an origin cancer site of patients (87%) with cancer with unknown primary origin.