The aim of this study is to describe the clinical features and define the prognostic significance of disease dissemination in a large series of nongastric marginal-zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. We studied 208 patients with nongastric marginal-zone B-cell MALT lymphoma diagnosed and treated from 1991 to 2004. Ninety percent of the patients had a single site of MALT involvement--skin (26%), salivary glands (18%), orbit (14%), Waldeyer's ring (13%)--and 39% and 28% had nodal involvement and bone marrow involvement, respectively. After a median follow-up of 2.7 years, the median event-free survival (EFS) time was 2.4 years, and the median overall survival (OS) time was not reached. On univariate analysis, the features significantly associated with longer EFS and OS times were the following: single MALT site involvement (OS), localized disease (EFS and OS), no nodal disease (EFS and OS), skin and orbit lymphoma (OS), and stage IV disease without bone marrow involvement (OS). On multivariate analysis, both bone marrow and nodal involvement were associated with shorter OS. This study describes the clinical features and the natural history of nongastric marginal-zone lymphomas and highlights that the dissemination to lymph nodes and bone marrow is associated with a poorer outcome.