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Genomic rearrangements in the MYClocus occur in ∼12% of lymphomas with diffuse large B-cell lymphoma (DLBCL) morphology and are associated with inferior outcome. Previous studies exploring MYCrearrangements have primarily used fluorescence in situ hybridization (FISH) assays to characterize break-apart status but have rarely examined breakpoint location, and in some cases have not examined partner identity. We performed targeted sequencing of MYC, BCL2, BCL6, and the immunoglobulin (IG) loci in 112 tumors with DLBCL morphology harboring MYCrearrangement. We characterized the location of the MYCrearrangement at base pair resolution and identified the partner in 88 cases. We observed a cluster of breakpoints upstream of the MYCcoding region and in intron 1 (the “genic cluster”). Genic cluster rearrangements were enriched for translocations involving IGH(80%), whereas nongenic rearrangements occurred mostly downstream of the MYCgene with a variety of partners, including IGLand IGK. Other recurrent partners included BCL6, ZCCHC7, and RFTN1, which has not previously been described as a MYCpartner. We compared 2 commercially available FISH break-apart assays for the MYClocus and observed discordant results in 32% of cases examined, including some with MYC-IGLand MYC-IGKrearrangements. In cases of high-grade B-cell lymphoma with MYCand BCL2and/or BCL6rearrangement (HGBL-DH), so-called “double-hit” lymphomas, the majority of MYCrearrangements had non-IGpartners (65%), with breakpoints outside the genic cluster (72%). In patients with de novo HGBL-DH of DLBCL morphology, MYC-IGrearrangements showed a trend toward inferior time to progression and overall survival compared with MYC–non-IGrearrangements. Our data reveal clinically relevant architecture of MYCrearrangements in lymphomas with DLBCL morphology.