Low-grade mucosa-associated lymphoid tissue (MALT) type B-cell lymphomas of the salivary gland arise in a background of myoepithelial sialadenitis (MESA), usually in association with Sjögren's syndrome. The distinction between benign MESA and early lymphoma has proved difficult using histological criteria alone and the significance of B-cell monoclonality in this respect is controversial. We have used immunohistochemistry and polymerase chain reaction (PCR) amplification of immunoglobulin heavy-chain VDJ regions to assess clonality in biopsies from 45 patients with lymphoid infiltration of the parotid. Sequential biopsies spanning 3-18 years were available from seven patients, three of whom had developed disseminated nodal B-cell lymphoma. In light of previous studies, each biopsy was additionally analyzed for the presence of t(14;18) and Epstein Barr Virus (EBV) DNA using PCR. Monoclonality was detected in 34/45 cases. Comparison of histology with clonality confirmed earlier suggestions that the emergence of an identifiable population of centrocyte-like B cells around ducts or epithelial islands correlated with monoclonality. In six of seven patients with sequential biopsies PCR fragments of identical size were amplified from each biopsy, suggesting that demonstrable monoclonality in "lymphoepithelial" lymphoproliferative lesions of the salivary gland is indicative of lymphoma. No t(14;18) chromosome translocations were identified; EBV sequences were detected in three of 45 cases.