p53 expression and MYC extra copies (MYC-EC) have been reported to serve as independent adverse prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of p53 expression in MYC-EC lymphomas has not been delineated. Conversely, CD99 expression has been shown to have a positive impact on survival in patients with germinal center-type DLBCL, yet nothing is reported about the impact of CD99 expression and MYC status. This is the first study to evaluate p53 expression in MYC-EC lymphomas and CD99 expression in relation to MYC status. We identified 122 patients diagnosed as having large B-cell lymphoma (44, MYC-negative; 29, MYC-EC; 23, MYC rearrangement; 22, MYC and BCL2 rearrangements; 4, MYC, BCL2, and BCL6 rearrangements). p53 expression significantly correlated with DLBCL with abnormal MYC status (MYC-EC, MYC rearrangement, and MYC overexpression), but adverse p53 prognostic effect was only seen with MYC-rearranged lymphoma. CD99 expression was significantly associated with MYC-negative DLBCL and had better prognostic impact on lymphoma-specific survival (LSS), but not on relapse-free survival and overall survival. Overall, patients with MYC-EC lymphoma had significantly worse relapse-free survival and LSS than did patients with MYC-negative lymphoma, yet better overall survival and LSS than did the patients with MYC-rearranged lymphoma. Thus, patients with MYC-EC lymphomas had prognostic features that were intermediate between MYC-negative and MYC-rearranged lymphomas. Lastly, high-intensity chemotherapy (either dose-adjusted rituximab and etoposide-prednisone-vincristine-cyclophosphamide-doxorubicin or rituximab and hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone treatment) did not improve survival in patients with MYC-EC and MYC-rearranged lymphoma when compared with rituximab-cyclophosphamide-hydroxydaunomycin-vincristine-prednisone therapy.