Diffuse large B cell lymphomas (DLCBL) are a group of lymphomas whose biologic and prognostic diversity has been recently well characterized. There is also morphologic heterogeneity, but the relevance of subclassification remains uncertain. The World Health Organization Classification states that pathologists have the choice to use only the term diffuse large B-cell lymphoma or to use one of the specific morphologic variants. The aim of the present study was to evaluate if there is an association between immunoblastic morphology and the immunophenotypic profile in DLBCL. Two observers reviewed 117 DLBCL cases. Cases of immunoblastic lymphoma and cases of centroblastic polymorphic lymphoma with more than 50% immunoblasts were defined as having immunoblastic morphology. Immunohistochemistry was performed on tissue microarray slides to establish the immunophenotypic profile. Patients with immunoblastic morphology more frequently had a non-GCB phenotype (94% vs 6%). This finding suggests that the morphological subclassification of DLBCL does have biological meaning, in line with recent evidence indicating that the immunoblastic morphology should not be overlooked in lymphoma classification.