OBJECTIVE The aim of this study was to investigate the correlation between cathepsin D (Cath-D) and estrogen receptor (ER)expression in breast cancer tissue and to explore the prognostic significance of their combined determination in breast carcinoma patients with positive axillary lymph nodes. METHODS One hundred and thirty-eight cases of breast carcinoma were examined by immunohistochemistry (IHC) and the results relating to patient follow-up analyzed.RESULTS The overall 5-year disease-free survival rate (DFS) was 60.9% (84/138) in the series. The positive rate of Cath-D expression in the tumor cells was 55.07% and the positive ER staining was 51.4%. A definite significant negative correlation was found between the positive rates for Cath-D and ER (r=-0.294, P=0.001) The Cath-D expression for the cases in clinical Stage Ⅱ, ≥10 positive-node and recurrence or distant metastasis, was higher than that those cases in clinical Stage Ⅱ with fewer node-metastasis and with 5 year DFS (χ2=13.926, P=0.000;χ2=13.070, P=0.001; χ2=10.545, P=0.001). However, there was no significant difference of Cath-D expression between 2 groups of patients with different ages or among the different histopathologic types of the nonspecific invasive carcinoma. In the combined examination of Cath-D and ER, the cases that were ER (+) and Cath-D (-) had the highest 5-year DFS compared to other situations. In contrast, the cases that were reversed in expression, ie, ER(-) and Cath-D(+), had a lower 5-year DFS.There was a significant difference between the 2 conditions (χ2=18.675,P=0.000).CONCLUSION A combined determination and analysis of Cath-D and ER expression may be more useful to establish a prognosis than the biological characteristics of carcinomas with positive lymph nodes.