Murine epidermal Langerhans cells (LC) synthesize and express E‐cadherin, a homophilic adhesion molecule that mediates adhesion of LC to keratinocytes in vitro. To determine if E‐cadherin expression is characteristic of LC or is a feature of all dendritic cells (DC), we studied DC from various lymphoid tissues and peripheral blood for reactivity with anti‐E‐cadherin monoclonal antibody. By flow cytometry, DC prepared from skin‐associated lymph nodes (LN) expressed E‐cadherin, whereas DC prepared from gut‐associated LN and spleen did not. However, direct comparison revealed that levels of E‐cadherin expressed by DC from skin‐associated LN were ∼fivefold lower than those expressed by freshly‐prepared LC. Immunohistochemical studies confirmed that E‐cadherin was expressed by DC in skin‐associated LN in situ, and demonstrated that the number of E‐cadherin+ DC in LN draining skin previously treated with the contact allergen 2,4,6‐trinitrochlorobenzene was increased relative to the number of E‐cadherin+ DC present in LN draining normal skin. DC propagated from the blood of cyclophosphamide‐treated mice in granulocyte/macrophage‐colony stimulating factor‐supplemented media also expressed E‐cadherin. E‐cadherin immunoprecipitated from DC co‐migrated in SDS polyacrylamide gels with that from fibroblasts transfected with murine E‐cadherin cDNA, and mRNA encoding extracellular and intracellular regions of E‐cadherin was present in DC propagated from blood. These results indicate that E‐cadherin expressed by murine dendritic cells is identical to E‐cadherin expressed by epithelial cells, and suggest that E‐cadherin represents a DC differentiation antigen characteristic of LC and lineage‐related cells (skin‐associated LN DC).