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To inspect the expression, characteristics, clinical prognostic value and the level of immune infiltration of Collagen Type XII Alpha 1 Chain (COL12A1) in breast cancer (BC) using bioinformatics. We investigated the expression of COL12A1 in breast cancer and normal breast tissues using Tumor IMmune Estimation Resource (TIMER2.0) and the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). The correlation between COL12A1 and overall survival (OS) was determined using Kaplan-Meier Plotter in BC. The correlation between COL12A1, immune infiltrating cells and immune checkpoints was detected via TIMER2.0. We found that the expression of COL12A1 was significantly higher in BC tissues than in normal tissues. A higher expression level of COL12A1 correlated with lymph node metastasis and worse OS in human epidermal growth factor receptor 2 (HER2)-enriched BC patients. Moreover, COL12A1 was positively correlated with M2 macrophages and immune checkpoint programmed cell death 1 ligand 2 (PDCD1LG2) but negatively correlated with activated natural killer (NK) cells and cluster of differentiation 8 (CD8)+ T cells in HER2-positive BC. COL12A1 might act as a biomarker indicating poor prognosis in HER2-enriched BC and correlate with immune infiltration in HER2-positive BC. [ABSTRACT FROM AUTHOR]