AIM: To detect the expression of B cell receptor signaling pathway (BCRSP) in lacrimal gland benign lymphoepithelial lesions (LGBLEL). METHODS: Gene microarray was used to compare whole-genome expression in lacrimal gland tissues from LGBLEL patients to tissues from orbital cavernous hemangioma (control tissues). Expression of BCRSP was confirmed by polymerase chain reaction (PCR) and immunohistochemistry. RESULTS: The expression of 22 genes of the BCRSP increased significantly in LGBLEL patients. PCR analysis showed that CD22, CR2, and BTK were all highly expressed in LGBLEL tissues. Immunohistochemical analysis showed that CR2 protein was present in LGBLEL, but CD22 and BTK proteins were negative. CR2, CD22, and BTK were not observed in the orbital cavernous hemangiomas with either PCR or immunohistochemistry. CONCLUSION: BCRSP might be involved in the pathogenesis of LGBLEL.