The aim of this study was to evaluate the correlation between serum tumor markers CEA and CA 15-3 in breast cancer (BC) patients with disease relapse and different prognostic parameters at first operation. Sixty-two women (median age 55 years, range 35-83 years) who had undergone curative surgery for pT1-2 pN0-1 M0 breast cancer developed local recurrences, distant metastases or contralateral BC during a median relapse time of 53 months (range 25-149 months). Sensitivity of CEA, CA 15-3, and CEA + CA 15-3 together was 40.3%, 41.9% and 59.7%, respectively. No correlation (p = NS) was found between tumor markers sensitivity and type of recurrence, surgical procedure, histologic subtypes and hormone receptors rate. CEA significantly (p < 0.01) correlated with the size of the tumor and axillary node status and CA 15-3 with the age of the patients. In conclusion, CEA and CA 15-3 should be considered complementary in detecting BC recurrences but their sensitivity is low and independent of the majority of the prognostic parameters that may be considered before relapse.