B-cell lymphomas with MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21), also known as double-hit or MYC/BCL2 B-cell lymphomas, are uncommon neoplasms. We report our experience with 60 cases: 52 MYC/BCL2 B-cell lymphomas and 8 tumors with extra MYC signals plus IGH@BCL2 or MYC rearrangement plus extra BCL2 signals/copies. There were 38 men and 22 women with a median age of 55 years. In all, 10 patients had antecedent/concurrent follicular lymphoma. Using the 2008 World Health Organization classification, there were 33 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (henceforth referred to as unclassifiable, aggressive B-cell lymphoma), 23 diffuse large B-cell lymphoma, 1 follicular lymphoma grade 3B, 1 follicular lymphoma plus diffuse large B-cell lymphoma, 1 B-lymphoblastic lymphoma, and 1 composite diffuse large B-cell lymphoma with B-lymphoblastic lymphoma. Using older classification systems, the 33 unclassifiable, aggressive B-cell lymphomas most closely resembled Burkitt-like lymphoma (n=24) or atypical Burkitt lymphoma with BCL2 expression (n=9). Of 48 cases assessed, 47 (98%) had a germinal center B-cell immunophenotype. Patients were treated with standard (n=23) or more aggressive chemotherapy regimens (n=34). Adequate follow-up was available for 57 patients: 26 died and 31 were alive. For the 52 patients with MYC/BCL2 lymphoma, the median overall survival was 18.6 months. Patients with antecedent/concurrent follicular lymphoma had median overall survival of 7.8 months. Elevated serum lactate dehydrogenase level, ≥2 extranodal sites, bone marrow or central nervous system involvement, and International Prognostic Index >2 were associated with worse overall survival (P<0.05). Morphological features did not correlate with prognosis. Patients with neoplasms characterized by extra MYC signals plus IGH@BCL2 (n=6) or MYC rearrangement with extra BCL2 signals (n=2) had overall survival ranging from 1.7 to 49 months, similar to patients with MYC/BCL2 lymphomas. We conclude that MYC/BCL2 lymphomas are clinically aggressive, irrespective of their morphological appearance, with a germinal center B-cell immunophenotype. Tumors with extra MYC signals plus IGH@BCL2 or MYC rearrangement plus extra BCL2 signals, respectively, appear to behave as poorly as MYC/BCL2 lymphomas, possibly expanding the disease spectrum.