Background: Several studies on single and double protein expressing DLBCL (DPL), defined as BCL2 positive in > 70% and MYC positive in > 40%, have identified inferior clinical outcomes when treated with standard RCHOP compared with non-expressing DLBCL. We present the clinical outcomes of patients with single protein expressing and DPL, in comparison with non-expressors of BCL2 or MYC, treated with REPOCH. Methods: We conducted a retrospective review of all consecutive, newly diagnosed DLBCL patients treated with REPOCH at MD Anderson Cancer Center from 2010 to 2014. Eligible patients were ≥ 18 years, had immunohistochemical (IHC) staining for MYC and BCL2, and had available data of demographics, pathology, treatment, and response. The objectives were to analyze demographics, response to therapy, and survival outcomes in comparison with MYC and BCL2 expression. Double hit lymphoma defined as MYC and BCL2 or 6 translocation were excluded from this analysis (Oki et al, British J Hematology 2014). Results: We identified DLBCL patients with IHC data for BCL2 (n = 151), MYC (n = 60), and both (n = 52). The demographic characteristics between the groups were similar (Table). The overall response rates (ORR), one and three year overall survival (OS) rates, and proportion of patients treated with dose adjusted EPOCH were not significantly different between patients with MYC + vs. -, BCL2 + vs. -, and DPL. In addition, ORR and OS were not different between DPL, MYC+BCL2-, MYC-BCL2+, or MYC-BCL2- patients. The median follow up time for censored observations was 2.8 years. Conclusions: In this large retrospective analysis of DLBCL patients treated with REPOCH, we identified that clinical outcomes with overexpression of MYC and/or BCL2 may not be inferior in comparison to DLBCL with lack of overexpression, though prospective studies are needed to confirm these data. Additional analyses are ongoing and will be presented at the ASCO meeting.