Saliva-based translational research and LEE011 technology is now at a mature juncture and can be evaluated to determine its utility for breast cancer detection. Explorative studies have evaluated the potential use of salivary proteins such as c-erbB-2, VEGF, EGF, and CEA in the initial detection and/ or follow-up screening for the recurrence of breast cancer. However, these investigations were not based on biomarker discoveries from saliva specimens, rather they were testing blood biomarkers in saliva. Here, we report the use of transcriptomic and proteomic approaches to discover and pre-validate biomarkers in saliva for the noninvasive detection of breast cancer. Our results demonstrate significant differences in salivary transcriptomic and proteomic profiles between breast cancer patients and controls. The discovered salivary biomarkers possess discriminatory power for the detection of breast cancer, with high specificity and sensitivity. Early detection of breast cancer offers the promise of easier treatment and improved survival. Conventional screening has a less-than-desirable sensitivity and specificity. Our long-term goal is to develop a saliva-based noninvasive tool for the early detection of breast cancer. We envision a clinical context in which a salivary test may enable clinicians to detect breast cancer earlier, and reduce the number of unnecessary biopsies, in a cost-effective manner. The purpose of this study, which is an essential step toward attaining our long-range goal, is to evaluate the potential utilityof salivary transcriptomes and proteomes for breast cancer detection. We applied two high-throughput technologies in order to assess 1) whether the salivary transcriptome and proteome profiles change with the onset of breast cancer, and 2) whether discriminatory biomarkers can be identified and validated. By addressing both questions, our profiling results, and further independent validation of the discovered biomarkers, will open new research directions and support the idea that saliva is a useful biomarker source for breast cancer detection. The salivary transcriptome is a novel diagnostic alphabet we have explored for discovering breast cancer biomarkers. Salivary transcriptional profiling technology has been successfully applied for discovering detection biomarkers of resectable pancreatic cancer. Consistent with that study, high-throughput profiling revealed significant variations in gene signature profiles between the breast cancer patients and the controls, demonstrating that the salivary transcriptome is an informative biomarker source for systemic cancer detection. The gene ontology analysis could categorize the 1301 up/down-regulated genes into various biological processes based on their known roles or functions. Proteomic profiling, without independent validation, has been recently performed for discovering salivary biomarkers using stimulated whole saliva.