To assess the potential of using oncoprotein levels in blood as a marker of breast cancer status, we measured ras p21 in blood samples taken from 34 breast cancer cases and 60 non-cancer controls including 26 women with benign breast disease (BBD) and 34 healthy women. Plasma samples drawn before surgery or at routine office visit were analyzed for ras p21 by Western blot with computer aided image analysis to measure staining intensity in integrated pixel units (IPU). We found detectable levels of ras p21 in 53% of the blood samples of cases, in 27% of the BBD controls and 26% of the healthy controls. Comparing cases to the combined control group (n=60) and controlling for known breast cancer risk factors, ras p21 was associated with breast cancer status (odds ratio=5.22, 95% CI=1.58-17.23). The median levels of ras p21 staining were higher in cases (7.04 IPU, P=0.03) compared to BBD controls (0.00 IPU) or healthy controls (0.00 IPU). The sensitivity of the assay for detecting breast cancer was 50% which compares favorably with that seen for erbB-2 ( approximately 10%), a more extensively studied blood-borne tumor marker. Ras p21 may be useful in the early detection of breast tumors and in post-surgical follow-up of patients, giving patients and physicians new tools for managing breast cancer.