Early detection of a growing breast tumor is of key importance for patient survival. Despite limitations, mammography screening has improved the detection of breast tumors, however many tumors are not detected. This is especially true for younger women and women with high breast density. Novel diagnostic blood biomarkers either generated by the tumor and released into the blood, or generated by nontumor cells as a response to the tumor presence, can now potentially help improve the accuracy of early-stage breast cancer detection. They include multicomponent biomarkers, circulating tumor cells and RNA expression of peripheral blood. These novel biomarkers and their potential use will be presented and discussed in this review, with special emphasis on gene expression-based markers.