Breast cancer is one of the leading causes of cancer death worldwide. This study aimed to analyze the expression of centromere protein H (CENP-H) in breast cancer and to correlate it with clinicopathologic data, including patient survival. Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells, immortalized mammary epithelial cell lines, and breast cancer cell lines, we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells. We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry, and detected high CENP-H expression in 134 (43.6%) samples. Statistical analysis showed that CENP-H expression was related with clinical stage (P = 0.001), T classification (P = 0.032), N classification (P = 0.018), and Ki-67 (P < 0.001). Patients with high CENP-H expression had short overall survival. Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival. Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.