Langerhans cell sarcoma (LCS) is a rare malignancy derived from dendritic cells of the epidermis that is characterized by cytological atypia, frequent mitoses, and aggressive clinical behavior. Cancer-associated B7 molecules including B7-H1, B7-DC, B7-H3 and B7-H4 are thought to be involved in the immunoescape of cancer cells and to function as prognostic markers. However, the expression and distribution of these molecules in LCS have not been described. Here we report that all of these molecules were observed in LCS sample sections by immunohistochemistry analysis. At the cellular level, they were found on the cell membrane and in the cytoplasm. Fluorescence dual staining indicated that B7-H1, B7-H3 and B7-H4 were principally associated with Langerin(+) tumor cells. More interestingly, B7-H1, B7-H3 and B7-H4 were co-expressed on the same tumor cells. Z39Ig, the novel B7-related protein, was also found in the LCS sample sections. Fluorescence dual staining showed that Z39Ig was restricted on CD68(+) macrophages. Our results suggest that B7-H1, B7-H3 and B7-H4 may be potential biomarkers to identify LCS, and a clear understanding of their functional roles may further elucidate the pathogenesis of this carcinoma and potentially contribute to the development of novel immunotherapeutic strategies.