Background: The transcription factor IRF4 (interferon regulating factor 4) regulates immunoglobulin class switch recombination as well as plasma cell differentiation. We examined the prognostic significance of IRF4 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for IRF4 (204562_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of IRF4 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes: luminal A (ER⁺/HER2^-/aurora kinase A [AURKA]^low, luminal B (ER⁺/HER2^-/AURKA^high), basal-like (ER^-/HER2^-), HER2⁺. Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of IRF4 was related to better MFS in a meta-analysis of the whole cohort (HR 0.49, 95% CI 0.35-0.69, P<0.0001). Prognostic significance was most pronounced in the HER2⁺ positive molecular subtype (HR 0.18, 95% CI 0.06-0.55, P=0.0008) as compared to luminal A (HR 0.75, 95% CI 0.36-1.53, P=0.425), luminal B (HR 0.39, 95% CI 0.20-0.76, P=0.0044) and basal-like (HR 0.55, 95% CI 0.32-0.94), P=0.0279) carcinomas of the breast. IRF4 showed independent prognostic significance (HR 0.394, 95% CI 0.249-0.621, P<0.0001) in multivariate analysis. In addition to IRF4, only histological grade of differentiation (HR 2.591, 95% CI 1.604-4.187, P<0.0001) and tumor size (HR 1.791, 95% CI 1.135-2.825, P=0.012), but neither age nor HER2 status nor hormone receptor status retained an independent prognostic association with MFS. Conclusions: The transcription factor IRF4 has independent prognostic significance in node-negative breast cancer. Higher expression of IRF4 is associated with improved outcome. The prognostic impact differs between diverse molecular subtypes and is most pronounced in HER2⁺ breast cancer.