Aims: This study is a clinical pilot study with the principal aim to investigate the accuracy of a panel of serum tumor markers for the early diagnosis of relapses. We propose a systematic use of serum CEA-TPA-CA15.3 tumor marker panel and criteria in order to make it an accurate tool for a postoperative breast cancer monitoring. Materials & methods: 204 disease free breast cancer patients after mastectomy were intensively monitored with serial serum determination of CEA, CA15.3 and TPA. Results: During a mean follow-up of 3.7 years the sensitivity of the CEA-TPA-CA15.3 tumor marker panel was 93%, the specificity was 97.6% and the rate of false ‘warning signals’ per year of follow-up was 9 per 100 patients. Conclusions: Our results show that the proposed tool is promising for a postoperative monitoring of breast cancer patients.