Low-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the salivary gland are usually indolent diseases with a protracted clinical course. Recurrent multifocal disease has been shown to represent identical clones in some cases, and intraclonal variation resulting from continuing somatic hypermutation has been described, but emergence of novel, major clones upon recurrent disease has not been documented. We analyzed three consecutive biopsy specimens of parotid lymphoid infiltrates of a young woman with Sjögren's disease. The immunoglobulin heavy chain (IgH) gene rearrangements were first amplified using FR2/LJH-VLJH consensus primers. Then, the PCR products were cloned, sequenced, and compared. On the basis of the sequences of the complementarity determining region 3 (CDR3), clone-specific primers were designed and used to evaluate the presence of similar sequences in different biopsy specimens. Recurrent parotid lymphoid infiltrates during a span of 9 years showed histologically similar features consistent with low-grade MALT lymphoma. Polymerase chain reaction amplification showed a clonal pattern of IgH gene rearrangement in all of the lesions with similar product sizes, suggesting the identity of the clones, but two major clones with different CDR3 sequences were found. Intraclonal variation was seen among the sequences seen in the three lesions consistent with the occurrence of somatic hypermutations. Primers specific to the clone seen in the first two lesions failed to amplify products from the third lesion, but primers specific to the third clone showed similar products in the second clone in a small quantity, indicating that this clone persisted and expanded. Our results suggest that different B-cell clones might dominate during the course of low-grade MALT lymphoma of the salivary gland. This implies that in some cases, these processes can represent oligoclonal B-cell proliferations.