The traditional view that immunoglobulin is produced only by differentiated B lymphocytes has been challenged as immunoglobulin genes have been found to be expressed in nonhematopoietic human cancer cells. However, this phenomenon has not been widely accepted, and knowledge about this newly discovered concept is limited. In this study, we investigated the IgG1 heavy chain (IGHG1) constant region gene and IgG protein expression in 6 cell lines, including epithelial cancer cells, and in tissues from 66 hyperplasias, adenomas, and carcinomas. We also studied the mechanism of IgG production in these cells by examining the expression of RAG1 (recombination activating gene 1), RAG2, and AID (activation-induced cytidine deaminase). In cancer cell lines, mRNA of the IGHG1 constant region and I-C sterile transcript were detected by nested RT-PCR, and Ig and Ig proteins were detected by immunofluorescence and Western blot. In surgically resected carcinoma tissues, we detected mRNA of the IGHG1 constant region by in situ hybridization, and by laser microdissection-assisted nested RT-PCR. Ig and Ig proteins were detected by immunohistochemistry. The V(D)J recombination of IgH and IgL loci, the S1/2-Sµ switch circle, and the expression of RAG1 and RAG2 were also found in these cancer cell lines. These data suggest that cancer cells are capable of producing IgG. Because of its potential biological and clinical significance, this phenomenon warrants further investigation.--Chen, Z. and Gu, J. Immunoglobulin G expression in carcinomas and cancer cell lines.