Objective To study the usefulness of combined detection of 4 tumor markers in patients with recrudescent and metastatic breast cancer. Methods The serum levels of CA153, CEA, TPS and CA125 were determined by chemiluminescence immunoassay. A total of 1245 subjects entered the study. Sensitivities of the tests were evaluated in 1 000 patients with breast cancer (102 preoperative patients and 898 postoperative patients) and 245 with benign breast disease. Results The serum levels of CA153, CEA and TPS were significantly elevated in preoperative patients compared with metastatic patients (Plt;0.001). The serum levels of CA153, CEA, TPS and CA125 were significantly elevated in metastatic patients compared with non-metastatic patients (Plt;0.001). The sensitivity of the 4 tumor markers were significantly elevated in metastatic patients compared with preoperative and postoperative non-metastatic patients (Plt;0.05). The sensitivity of combined detection of the 4 tumor markers were 56.72% and 94.68% in preoperative patients and metastatic patients, respectively. The CEA elevation was bly correlated with CA153 and TPS levels (all P=0.000 1, r=0.410 and 0.396, respectively). Conclusion Combined detection of the 4 tumor markers may play a guiding role in post-therapeutic monitoring of breast cancer in progressive, recrudescent and metastatic patients.