Myoepithelial sialadenitis (MESA) can often be difficult to distinguish from low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). The authors have previously studied a series of 25 patients with MESA and identified histologic and immunologic features predictive of extrasalivary lymphoma (ESL). The authors have now analyzed formalin-fixed, paraffin-embedded salivary gland tissue from 21 of these patients (and 1 new patient) for immunoglobulin heavy chain (IgH) gene rearrangement by a semi-nested polymerase chain reaction (PCR) technique to compare monoclonality by IgH PCR with clinical outcome (median follow-up 6.7 years, range 3 months-19.4 years) and the paraffin section immunophenotype. The PCR technique employed consensus primers from variable (FR3A) and joining regions (LJH, VLJH) of the IgH gene. A monoclonal PCR product was detected in 16 of 28 specimens from 13 of 22 patients. By Fisher's exact test, a monoclonal PCR pattern did not correlate (P > .05) with development of ESL, broad strands of monocytoid B-cells, plasma cell light chain restriction by immunoperoxidase, or CD43 coexpression on monocytoid B cells by immunoperoxidase. This study suggests that the majority of MESA lesions harbor monoclonal B-cell populations and that clonality does not predict progression to clinically overt lymphoma. Acquired salivary gland MALT, in the form of MESA, may progress to a process that is clonal but not necessarily malignant. Extranodal lymphoma develops in a minority of patients with this lesion.