The development of modern molecular biology techniques and their use in characterizing the genetic abnormalities that are of pathogenic significance in non-Hodgkin’s lymphoma (NHL) now provides a means to diagnose and rationally subcategorize these neoplasms in addition to the more traditional use of morphologic and immunophenotypic criteria. The shortcomings of traditional methods of NHL diagnosis and classification have been especially evident within the morphological subset commonly referred to as the large-cell lymphomas, which comprise approx 25% and 40% of NHL in children and adults, respectively (1 ). The marked cytological, immunological, and clinical heterogeneity of this group of tumors suggests that it is comprised of several biologically different neoplasms, but morphological and immunophenotypic subclassification schema have failed to identify meaningful subsets within the large-cell lymphomas. Recently, however, two recurrent genetic abnormalities in large-cell NHL-activation of the BCL6/LAZ3 zinc finger gene located at 3q27 (altered in approx 30% of large-cell lymphomas [2 –4 ]) and the NPM-ALK fusion gene (5 –7 ) produced by the t(2;5)-have been analyzed to now permit the identification of patient subsets that have reproducibly different therapeutic responses and survival rates in most studies, both of these molecular genetic subtypes appearing to have a superior prognosis compared to those cases lacking these gene abnormalities.