In order to define the most useful tumor marker panel in breast cancer patients' follow-up and in monitoring treatment response, serological levels of CEA, MCA, Ca 15-3 and Ca 27-29 were evaluated in 220 patients. 180 patients had no evidence of disease (NED) after primary treatment, and 40 had metastases at first diagnosis time; in a 4 years follow-up, 30 of the NED patients relapsed, and were then included in the group of metastatic patients subjected to anticancer treatment. Overall sensitivity in metastatic patients was: CEA 40%, MCA 35%, Ca 15-3 79%, Ca 27-29 70%, with the highest percentages and mean values in liver and bone localizations. Combination of Ca 15-3 and Ca 27-29 improved sensitivity in bone lesion (85% vs 80%), in locoregional relapses only association with CEA increased sensitivity (60% vs 40%). Ca 15-3 and Ca 27-29 values increased on average 3 months before clinical diagnosis. In treated patients there was a better correlation with a clinical course of disease for Ca 15-3 and Ca 27-29 (both 81%) as compared to the other determined markers.