Dectin‐2 is a recently described dendritic‐cell‐associated receptor, suggested to be involved in the initiation and maintenance of UV‐induced tolerance. To understand the physiological relevance of the proposed functions of this C‐type lectin‐like receptor, we have generated monoclonal antibodies against its extracellular domain and performed a detailed study of its expression. In naive mice, Dectin‐2 has a novel distribution pattern compared with other myeloid markers, but is predominantly expressed by a wide variety of tissue macrophages. Its expression was limited on dendritic cells and notably absent from brain microglia and choroid plexus or meningeal macrophages. On peripheral blood monocytes, Dectin‐2 expression was very low on the surface but was transiently and markedly up‐regulated on induction of inflammation in vivo using a variety of stimuli. This change in Dectin‐2 expression occurs on ‘inflammatory’ monocytes after arrival at the inflammatory lesion as demonstrated by adoptive cell‐transfer studies, and is independent of whether the macrophages elicited by the stimuli ultimately expressed Dectin‐2. These observations show Dectin‐2 expression to be characteristic of monocyte activation/maturation at an inflammatory lesion and provide a new perspective on the interpretation of Dectin‐2 function in vivo.