To analyse the possible activation of distinct molecular pathways in mucosa-associated lymphoid tissue (MALT) lymphoma, we determined the prevalence of trisomies 3, 12, 18 in MALT lymphomas from different organs, as well as the prevalence of translocations of the MALT1 gene in a subset of primary breast MALT lymphomas. We compared the numerical cytogenetic alterations in lymphomas, precursor lesions and in normal non-haematolymphoid tissue from the same organs. Forty-two samples of paraffin-embedded tissue (29 MALT lymphomas from stomach, breast, parotid and thyroid; two Sjögren's syndrome; two Hashimoto's thyroiditis and nine reactive samples) were studied by fluorescence in situ hybridization (FISH). Analysed together, the cases of gastric, parotid and thyroid MALT lymphomas presented trisomy 3 in 46%, trisomy 12 in 28% and trisomy 18 in 21% of the cases. In contrast to other locations, trisomy 3 was not present in the majority of the cases of primary breast MALT lymphomas. None of the nine breast cases presented MALT1 gene rearrangements. Half of the cases of preneoplastic lesions exhibited trisomy 3 and trisomy 12; none exhibited trisomy 18. Trisomy 3 is the most frequent numerical abnormality in gastric, parotid and thyroid but not in primary breast MALT lymphomas. MALT1 gene rearrangements are also rare in this location, suggesting that distinct molecular pathways may be activated in breast cases.