In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure. In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched.