Triggering receptor expressed on myeloid cells 1 (TREM‐1) is an activating receptor involved in inflammatory diseases and septic shock. The TREM‐1 ligand(s) (TREM‐1L) have not yet been identified. In this study, we performed a detailed analysis of the expression of mouse TREM‐1 and its ligand(s). Our results demonstrate that TREM‐1 is expressed on bone‐marrow‐derived dendritic cells (BMDC). On bone‐marrow‐derived macrophages (BMM) its expression is induced in vitro after stimulation by granulocyte–macrophage colony‐stimulating factor, interleukin‐3 or by myeloid differentiation primary response gene 88 (MyD88)‐dependent Toll‐like receptor (TLR) ligands. Under steady‐state conditions mouse TREM‐1 is detectable on a Gr‐1⁻ F4/80⁺ monocyte subpopulation bearing markers of resident monocytes, but not on Gr‐1⁺ F4/80⁺ inflammatory monocytes. During lipopolysaccharide (LPS)‐induced endotoxaemia TREM‐1 was also up‐regulated on inflammatory Gr‐1⁺ F4/80⁺ cells in vivo. In tumour‐bearing mice, TREM‐1 was up‐regulated on Gr‐1⁺ F4/80⁺ monocytes, which phenotypically and functionally resembled mononuclear myeloid‐derived suppressor cells. Using a soluble TREM‐1 fusion protein, we demonstrate that after intravenous injection of LPS TREM‐1L was induced on Gr‐1⁺ granulocytes and monocytes but not on other cell populations in peripheral blood. This up‐regulation on granulocytes was directly mediated by TLR ligands and required the adapter protein MyD88. In contrast to human, mouse platelets expressed TREM‐1L neither under steady‐state conditions nor after LPS injection in vivo. Our study reveals differential regulation of TREM‐1 expression on mouse monocyte subpopulations and improves our understanding of the biological role of TREM‐1 during disease.