Among the diffuse lymphomas of B-cell origin, we have encountered one variant displaying blastoid features that morphologically mimic lymphoblastic lymphoma, the blastoid variant of mantle cell lymphoma, and the so-called blastoid transformation of follicular lymphoma. To better characterize this entity, we studied eight cases morphologically, immunohistochemically, and by fluorescence in situ hybridization (FISH) for cytogenetic abnormalities commonly associated with follicular lymphoma and B-cell lymphomas exhibiting high-grade histological features. All eight cases were presented as de novo neoplasms, and displayed an entirely diffuse (five cases) or only minimal follicular (three cases) growth pattern. The neoplastic lymphoid cells were of medium size with round nuclei, fine chromatin, inconspicuous nucleoli, and high mitotic rate; they expressed CD10, BCL6, and BCL2-a phenotype consistent with follicle center cell origin. A proportion of cases expressed MUM1. Their lack of TdT and CYCLIN D1 distinguished them from lymphoblastic lymphoma and the blastoid mantle cell lymphoma, respectively. The neoplastic lymphoid cells consistently expressed CD43 (seven of eight cases) and occasionally other T-cell-associated antigens, including CD5, CD7, CD8, and CD57. Although all cases overexpressed BCL2, t(14;18) was not detected in any of the five cases examined by FISH; instead, extra copies of chromosome 18 were found in four of five cases. Finally, other cytogenetic abnormalities, including structural abnormalities of BCL6 (allelic loss/gain, rearrangement), monosomy 7, del(13)(q14), and MYC allelic loss, were frequently detected. The combination of a B-cell CD10+ BCL6+ BCL2+ phenotype in the presence of structural abnormalities of BCL6 is consistent with a follicular center cell derivation for our cases. The lack of t(14;18) seen in our cases, although rare in most cases of follicular lymphoma, has been nevertheless reported in cases of follicular lymphoma with a predominantly diffuse growth pattern. The molecular pathogenesis, clinical manifestations, and prognostic significance of these lesions remain to be elucidated.