PURPOSE: Histone deacetylase 6 (HDAC6) is an enzyme that deacetylates heat-shock protein 90 (HSP90). Many studies have investigated the role of HDAC6 and HSP90 in tumorigenesis and in the prognosis of cancer patients. This study aimed to evaluate the prognostic value of HDAC6 and acetylated HSP90 (acetyl-HSP90) in a cohort of breast cancer patients. METHODS: Immunohistochemical analysis of 314 surgical specimens obtained from patients with invasive breast cancer was carried out to assess standard pathologic factors and the expression of HDAC6 and acetyl-HSP90. Statistical analyses were performed to determine the association between HDAC6, acetyl-HSP90, and conventional clinicopathological factors, and the prognostic values of these factors were evaluated. RESULTS: HDAC6 expression did not show any correlation with other clinicopathological factors, but acetyl-HSP90 was significantly correlated with histologic grade (p=0.001) and the Ki-67 index (p=0.015). HDAC6 and acetyl-HSP90 expression were significantly associated with each other (p=0.047). Although HDAC6 was not prognostic for disease-free survival (DFS), some patients with high expression of HDAC6 experienced recurrence 5 years after diagnosis, while there was no recurrent disease after 5 years in those with low expression. Acetyl-HSP90 was significantly associated with the DFS of all patients (p=0.016) and with high HDAC6 expression (p=0.017), but not with low expression. CONCLUSION: Expression of HDAC6 and acetyl-HSP90 are correlated. HDAC6 is proposed to be a possible predictive marker of late recurrence, and acetyl-HSP90 has prognostic value in predicting the DFS of breast cancer patients.