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Background: A20 protein has ubiquitin-editing activities and acts as a key regulator of inflammation and immunity. Previously, our group showed that A20 promotes tumor metastasis through multi-monoubiquitylation of SNAIL1 in basal-like breast cancer. Here, we investigated survival outcomes in patients with breast cancer according to A20 expression. Patients and methods: We retrospectively collected tumor samples from patients with breast cancer. Immunohistochemistry (IHC) with an A20-specific antibody was performed, and survival outcomes were analyzed. Results: A20 expression was evaluated in 442 patients. High A20 expression was associated with advanced anatomical stage and young age. High A20 expression showed significantly inferior recurrence-free-survival and overall-survival (P<0.001 and P<0.001, respectively). Multivariate analysis showed that A20 was an independent prognostic marker for RFS (HRs: 2.324, 95% CIs: 1.446–3.736) and OS (HRs: 2.629, 95% CIs: 1.585–4.361). In human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) subtypes, high A20 levels were associated with poor OS. Conclusion: We found that A20 expression is a poor prognostic marker in breast cancer. The prognostic impact of A20 was pronounced in aggressive tumors, such as HER2-positive and TNBC subtypes. Our findings suggested that A20 may be a valuable target in patients with aggressive breast cancer. [ABSTRACT FROM AUTHOR]