AimsTo assess how hybridization probe design may affect MYC status determination in Burkitt lymphoma and diffuse large B‐cell lymphoma.Methods and resultsWe compared the results obtained with one dual‐fusion and two break‐apart commercial probes in a retrospective series of 91 aggressive B‐cell lymphomas. All three probes were able to detect the IGH–MYC translocation in every case bearing it (13/13). However, seven of 13 (54%) non‐IGH–MYC (light‐chain immunoglobulin or non‐immunoglobulin‐MYC) rearrangements were unambiguously detected by just one of the probes tested. On the other hand, when the IGH–MYC dual‐fusion probe was used, nine of 15 (60%) cases with a hybridization pattern suggestive of a non‐IGH–MYC translocation were attributable to MYC copy gain rather than MYC rearrangement, as demonstrated by both break‐apart probes.ConclusionsTaking into account the prognostic and therapeutic implications of the MYC translocation, probe design and limitations should be particularly kept in mind when MYC hybridization patterns are interpreted. In our experience, detection of 8q24 abnormalities could be optimized by a two‐probe approach involving the application of both IGH–MYC dual‐fusion and MYC break‐apart selected kits.