The distinction between Burkitt (BL) or atypical Burkitt/Burkitt-like lymphomas harboring a MYC translocation (MYC+) and diffuse large B-cell lymphomas (DLBCLs) with high proliferation fractions but without a MYC translocation (MYC-) can be difficult using standard morphologic and immunohistochemical criteria. Recently, unique gene expression profiles differentiating BL and DLBCL were reported and include higher transcript levels of T-cell leukemia-1 (TCL1) and CD38 and lower transcript levels of CD44 in MYC+ BL relative to MYC- DLBCL. We examined a cohort of 67 cytogenetically defined aggressive lymphomas using immunohistochemical techniques for expression of TCL1, CD38, and CD44 and found distinct expression patterns between MYC+ and MYC- tumors. Furthermore, these markers are better predictors of MYC status than combined staining for CD10 and BCL2. Thus staining for TCL1, CD38, and CD44 are useful ancillary tests to identify B-cell tumors for which confirmatory cytogenetic and/or fluorescent in situ hybridization studies assessing the status of the MYC locus should be pursued.