Unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) is a recently recognized category of mature B-cell lymphoma. This represents a heterogeneous group of diseases which often pose diagnostic problems in clinical practice, yet its distinction from DLBCL to BL is important for its therapeutic and prognostic implications. We report the challenging diagnostic process of a 60-year-old man. He had a CD10 and BCL2-positive, BCL6-negative B-cell malignancy with loss of multiple B-cell markers including surface immunoglobulin. The karyotype was complex and unusual, including t(2;18)(p12;q21), t(8;14)(q24;q32) and a derivative chromosome 22 mimicking a Philadelphia chromosome that led to initial diagnostic confusion. A triple-hit gray zone B-cell lymphoma with rearrangements of MYC, BCL2, BCL6, both alleles of IGH and likely IGK and IGL was finally diagnosed upon additional fluorescence in situ hybridization (FISH) studies. His disease was nonresponsive to intensive combination chemotherapy and he died 4 months after presentation. This case illustrates the diagnostic difficulty encountered in such group of B-cell lymphomas and emphasizes the need to integrate morphological, immunophenotypic and genetic data in making a diagnosis.