The importance of the extent of metastatic disease in the circulating levels of CA 15-3 and carcinoembryonic antigens (CEA) was studied in 173 patients with advanced breast carcinoma. Estimates of the extent of metastatic disease were obtained by an objective arbitrary scale. Patients were observed clinically after serum samples were obtained, and survival was recorded. Elevated values of CA 15-3 (greater than 40 U/ml) were seen in 130 patients and CEA values (greater than 5 ng/ml) in 97 cases (75% versus 56%, P less than .0001). Elevated CA 15-3 values correlated with the estimated extent of metastatic disease (P less than .0001), number of metastases (P = .0006), and survival from study entry (P = .01). Elevated CEA values correlated with extent of disease (P less than .0001), but not with the number of metastases or with survival. No correlation was found between the elevated values of CA 15-3 or CEA and age, menopausal status, and initial tumor size or nodal status. The combination of the elevated values of CA 15-3 and CEA was more sensitive than CA 15-3 alone (P = .04), but there were no significant improvements when subgroups were considered. Significant differences, that depended on which specific organ was affected dominantly by metastases, were seen in the mean levels of CA 15-3 antigen. Similarly, patients with liver involvement had higher mean levels of CA 15-3 than those without hepatic metastases. A stepwise regression analysis of the dominant site of metastases, liver involvement, and estimated extent of disease showed that only the latter parameter retained a significant correlation with CA 15-3 antigen levels (P less than .0001). Median survival of patients who showed abnormal CA 15-3 levels was significantly shorter than that of patients with nonelevated CA 15-3 (10.1 versus 18.0 months, P = .04). This difference was not appreciated with CEA levels (10.2 versus 12.2 months, P = .4). We conclude that tumor marker levels in patients with advanced breast carcinoma correlate with the extent of metastatic disease. In addition, the CA 15-3 assay is more sensitive and correlates more accurately with the extent of disease than CEA. Finally, the observed CA 15-3 differences by organ involvement are related to the extent of disease variations. The objective evaluation of the extent of metastatic disease provides a new approach in the study and comparison of breast cancer-associated tumor markers.