Rearrangement of the proto-oncogene MYC leads to MYC protein deregulation and is an important driver of oncogenic transformation. MYC rearrangement is a recurring genetic abnormality in several aggressive B-cell lymphomas including: Burkitt lymphoma, diffuse large B-cell lymphoma; B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma; rare de novo acute lymphoblastic lymphoma/leukemia, transformed follicular lymphoma, and plasmablastic lymphoma. Important distinctions in the role of MYC in these tumors likely reflect whether it is a primary or secondary genetic event. The presence of a MYC rearrangement in these diseases has diagnostic and prognostic implications and it is important for the practicing anatomic pathologist to be familiar with these issues when diagnosing aggressive B-cell lymphomas. This review provides a brief overview of MYC biology; shows the clinical and pathologic features of the aggressive B-cell lymphomas that harbor recurrent MYC rearrangements; explores the diagnostic and clinical implications of MYC rearrangements in these diseases; and outlines the techniques available to the anatomic pathologist to detect MYC deregulation.