Simple SummaryYY1 and CP2c is a transcription factor that regulates epigenetic pathways and protein modifications among several kinds of cancer. However, it is still unknown whether YY1 expression has any prognostic significance in patients with breast cancer. Thus, we investigated YY1 expression in association with CP2c in breast cancer patients and their prognostic implications. In this study, quantitative analysis of YY1 and CP2c expression in tumors revealed a negative correlation between them. Patients with YY1-high/CP2c-low expression showed the most favorable survival outcomes. YY1 overexpression was found to be significantly associated with a better prognosis after multivariate analysis. Our study provides novel findings about the association between YY1 and CP2c and its prognostic implication in breast cancer through quantitative analysis at the transcriptome and protein levels.AbstractYin Yang 1 (YY1) is a transcription factor that regulates epigenetic pathways and protein modifications. CP2c is a transcription factor that functions as an oncogene to regulate cell proliferation. YY1 is known to interact with CP2c to suppress CP2c’s transcriptional activity. This study aimed to investigate YY1 and CP2c expression in breast cancer and prognostic implications. In this study, YY1 and CP2c expression was evaluated using immunohistochemical staining, Western blot and RT-PCR assays. Of 491 patients with primary breast cancer, 138 patients showed YY1 overexpression. Luminal subtype and early stage were associated with overexpression (p< 0.001). After a median follow-up of 68 months, YY1 overexpression was found to be associated with a better prognosis (disease-free survival rates of 92.0% vs. 79.2%,p= 0.014). In Cox proportional hazards model, YY1 overexpression functioned as an independent prognostic factor after adjustment of hormone receptor/HER2 status and tumor size (hazard ratio of 0.50, 95% CI 0.26–0.98,p= 0.042). Quantitative analysis of YY1 and CP2c protein expression in tumors revealed a negative correlation between them. In conclusion, YY1 overexpression is a favorable prognostic biomarker in patients with breast cancer, and it has a negative correlation with CP2c at the protein level.