Tripartite motif (TRIM) family proteins are involved in various biological processes and the pathophysiology of cancers. However, the roles of TRIM39, a TRIM family member, in breast cancer is not well-understood. Here, we performed immunohistochemical study of TRIM39 protein in clinical estrogen receptor-positive (ER+) breast cancer tissues from 108 patients. TRIM39 immunoreactivity (IR) was positively correlated with advanced stage (p < 0.001), large invasive tumor size (p = 0.012), and positive lymph node status (p = 0.002). Positive TRIM39 IR was significantly correlated with short disease-free survival (DFS) (p = 0.001). Multivariate analysis revealed that the TRIM39 status is an independent prognostic factor in DFS (p = 0.049). Microarray analysis of MCF-7 breast cancer cells treated with siRNA revealed that TRIM39 knockdown downregulated the cell cycle- and cell division-related genes, including MLLT11, CDCA3, CDC25C, BIRC5, and ANP32E. Consistently, TRIM39 knockdown significantly suppressed proliferation and cell cycle transition to S phase in MCF-7 and 4-hydroxytamoxifen-resistant (OHTR) breast cancer cells. These results suggest that TRIM39 promotes ER+ breast cancer growth by promoting cell cycle progression.