Evaluation of a radioimmunoassay for a new tumor marker, named CA 27.29, recently proposed for use in breast cancer patients, is reported in this study. After considering the analytical performance, the clinical study was directed to a control group of 66 apparently healthy subjects (Controls), a group of 25 women with benign breast disease (BBD) and a group of 164 breast cancer patients divided into primary before any treatment (M-), in follow-up with no evidence of disease (NED) and presence of metastases (M+). When compared to CA 15.3, our results showed similar sensitivity of both markers with a slightly lower specificity for CA 27.29. In some cases, however, CA 27.29 elevation appears earlier than CA 15.3 as a sign of metastases. We thus propose their associated use.