Langerin is a type II transmembrane C-type lectin associated with the formation of Birbeck granules in Langerhans cells. The demonstration of langerin immunoreactivity is considered an adjunct or alternative to CD1a antigen expression as evidence to aid in the diagnosis of Langerhans cell histiocytosis. Evaluation of langerin expression is valuable in circumstances where a diagnosis of Langerhans cell histiocytosis is suspected, but cannot be confirmed due to lack of CD1a immunoreactivity. A panel of antibodies against CD1a, langerin, CD21, CD23, CD35 and S100 is very useful in the distinction of Langerhans cell histiocytosis, histiocytic sarcoma, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, disseminated juvenile xanthogranuloma, and Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy).