PURPOSE: The aim of this study was to investigate the expression and clinical implications of CCN family member 5 (CCN5) and the oestrogen receptor (ER) in advanced breast cancer (BC). METHODS: A total of 130 patients with advanced BC were selected for the study. Samples of normal breast tissue, ductal carcinoma in situ (DCIS), and invasive carcinoma were collected. The expression levels of CCN5 and ER in these tissues were examined using immunohistochemical methods. The correlation between expression of CCN5 and ER in different tissues and also differences in expression in invasive carcinoma were analysed. In addition, the relationship between CCN5 expression in advanced BC tissues and clinical pathological features was examined. RESULTS: CCN5 and ER had low expression in normal breast tissues and invasive carcinoma tissues, but high expression in DCIS, with this difference being statistically significant (X CONCLUSION: High expression of CCN5 and ER was observed in DCIS tissues of patients with advanced BC, with their expression being positively correlated. These findings suggest that CCN5 and ER may have a potential synergistic role in the progression of BC that influences the progression of advanced BC and can also be used to predict the effectiveness of endocrine therapy.