There is a wide spectrum of lymphoid hyperplasias and neoplasias that may arise in salivary gland tissue. Some lesions arise in the extranodal mucosal-associated lymphoid tissue (MALT) located in the salivary gland; others arise within the lymph nodes embedded in the gland parenchyma. It is difficult to distinguish the site and cell of origin in many salivary gland lymphoid lesions, but recent advances in the identification of specific gene rearrangements in lymphomas corresponding to normal follicular center cells have provided a molecular marker for these tumors. The genes involved are the immunoglobulin heavy chain gene (located on chromosome 14) and the blc-2 gene (located on chromosome 18). This specific chromosomal translocation [t(14;18)] has been sought in extranodal lymphomas of skin, stomach, and intestine. To date, primary lymphomas in these sites have lacked the t(14;18) translocation. We investigated the t(14;18) using molecular techniques in a series of morphologically and immunophenotypically defined malignant non-Hodgkin's lymphomas presenting in the salivary gland. Of the seven cases we examined, three had molecular evidence of a t(14;18) translocation. All three lesions had a nodular growth pattern. The four cases lacking bcl-2 rearrangement had diffuse growth patterns. In addition, all four bcl-2 germline cases had morphologic or clinical findings consistent with a MALT origin. In contrast to the data published to date for primary lymphomas of the stomach, skin, and intestine, our findings indicate that salivary gland lymphomas frequently contain bcl-2 gene rearrangement. In addition, there appear to be differences in the clinical findings of bcl-2 rearranged and bcl-2 germline salivary gland lymphomas.