MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy. Thirteen of 14 patients with available karyotyping data had a complex karyotype. In 8 cases the partner chromosome locus was an IG locus: t(8;14) (n=7) and t(8;22) (n=1). When MYC rearrangement was detected, most patients had a high-risk MCL international prognostic index, and the lymphoma cells had histologically aggressive features. Immunophenotypic analysis showed that the lymphoma cells were positive for cyclin D1 (n=16/16), Myc (9/11), and P53 (n=9/9). The Ki-67 proliferation rate was high (≥60%) in 10/11 cases. All patients received chemotherapy. The median follow-up time was 23 months. Clinical follow-up was available for 14 patients and treatment response in 13 patients. Eleven of 13 patients had refractory or relapsed disease, and 11 patients died. In conclusion, MCL with MYC rearrangement is characterized by advanced-stage disease, aggressive morphologic features, a high proliferation rate, p53 expression, a complex karyotype, and a poor prognosis. We believe these neoplasms fit within the overall concept of double-hit lymphoma, and the designation double-hit MCL may be helpful. We also believe that MYC rearrangement in MCL conveys important prognostic information that should be incorporated into the pathology report.