BACKGROUND The modification of histone acetylation and deacetylation is the most important mechanism of chromatin remodeling. These modifications are a subset of epigenetic alterations which affect tumorigenesis and progression through changes in gene expression and cell growth. Results of histone modification studies prompted us to explore the therapeutic and prognostic significance of histone deacetylase 3 (HDAC3) expression in patients with breast cancer. MATERIAL AND METHODS Immunohistochemical (IHC) staining was used to detect HDAC3 expression in a tissue microarray (TMA) that included 145 patients diagnosed with invasive ductal breast carcinoma. IHC scoring was used to evaluate the staining intensity and the proportion of positive cells. RESULTS HDAC3 expression was significantly correlated with estrogen receptor (ER)-negative expression (P=0.036) and progesterone receptor (PR)-negative expression (P=0.024). Additionally, HDAC3 expression was significantly positively correlated with human epidermal growth factor 2 (HER2) overexpression (P=0.037). Our study also indicated that high expression of HDAC3 was more frequently observed in breast tumors with PT2 classification (74%) versus PT1 (50.0%) and PT3 (71.4%) (P=0.040). Furthermore, HDAC3 was correlated with clinical stage II (P=0.046). Univariate and multivariate survival analyses showed that high expression of HDAC3 was correlated with poor overall survival (OS) (P=0.029 and P=0.033, respectively) in patients without lymph node involvement. CONCLUSIONS High HDAC3 expression is closely correlated with ER-negative expression, PR-negative expression, HER2 overexpression, PT stage, and clinical stage of breast tumors. HDAC3 may be an appropriate prognostic indicator in patients with invasive ductal breast cancer.