2 Background: Breast cancer accounts for 27% of female cancers. One in every eight women will develop breast cancer in their lifetime. More than 220,000 new cases of breast cancer will be diagnosed in the United States in 2020. Five-year survival rates for breast cancer are 98% for localized disease, 83% for regionally spread and 26% for distantly spread cancer. However, 25% of all metastases occur more than 5 years after the initial diagnosis and thus survival rates decrease as time goes out to 10 years due to disease recurrence. Current detection methods rely on imaging modalities, including mammography and MRI. No serum bio-markers have been approved for either breast cancer screening or monitoring for disease recurrence, yet. In asymptomatic women in remission from breast cancer the guidelines of the major oncologic organizations only suggest annual mammography for detection of new primary tumors. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a serum bio-marker for cancer. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including breast cancer. It has been detected by IHC in > 99% of tumor specimens tested (n > 2000) but is absent in adjacent non-affected tissue, and in tissue samples from non-affected individuals. This led to the development of a sandwich ELISA that reliably measures AABH in serum. Results: In the current study we have utilized the assay to quantify AABH levels in the sera of patients diagnosed with Breast Cancer compared to women free of disease. Increased levels of AABH were found in the serum of 99% of patients with breast cancer (n = 189). In women not known to have cancer, AABH was essentially undetectable in serum (n = 65, specificity = 96%). Serum from several women currently in remission subsequent to treatment for breast cancer were also analyzed and found to be negative for AABH. Conclusions: Thus, measurement of serum AABH levels has great promise as a diagnostic tool for breast cancer with potential application in monitoring for disease recurrence. Elevated serum AABH in conjunction with mammography and MRI may greatly facilitate earlier diagnosis of both primary and recurrent Breast Cancer.