Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal B-cell tumors that generally follow an indolent course. The gastrointestinal tract is the most common site of MALT lymphoma, comprising 50% of all cases. The tissue lesions are often localized, have high therapeutic response rates with late relapses with a long overall survival (OS). The patients with non-gastric lesions may follow a different clinical course and many of them present with disseminated disease. This study reports a series of 51 patients with non-gastric MALT lymphoma. Twenty patients (39.2%) presented with disseminated disease, seven (13.7%) patients had two MALT mucosal sites involved and eight (15.7%) had involvement of three or more mucosal sites. At presentation, 17 (33.3%) patients had the lymph node and 12 (23.5%) the bone marrow involvement. Following various combinations of treatment, complete remission was achieved in 40 (81.6%), and partial remission in three of the 49 treated patients with no difference in response rates between different disease stages. Relapse occurred in 12/43 (27.9%) patients among whom eight (18.6%) recurred in the presenting organ system. Five patients (9.8%) died because of a rapid disease progression after a median follow-up of 56 months; two patients with primary lung lesions, 1 patient with secondary intestinal disease, and 2 patients suffered transformation to diffuse large B-cell lymphoma. No significant difference in survival was found between localized and disseminated disease (log rank 0.05, df = 1, P = 0.81). A patient age > or = 60 yr at diagnosis and presentation with the nodal disease were found to be statistically significant negative prognostic factors (P < 0.05). Median OS was not reached after 145 months of follow-up, with the estimated OS being 88% at 2 yr, and 78% at 5 yr.