Primary mediastinal large B-cell lymphoma (PMLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that has distinct clinical and molecular features. PMLBCL is characterized by a locally invasive anterior mediastinal mass. Salvage therapy for recurrence or progressive disease is of limited efficacy; thus, the imperative is to cure at the first attempt when possible. The best reported outcomes in PMBL have been achieved with regimens that have incorporated radiotherapy in their planned primary treatment. Univariate and multivariate analysis in two retrospective series have suggested that receiving radiotherapy correlated to better event-free survival or OS. Distinction is needed between those that have residual disease and those that have simple fibrotic tissue. PET scan has become the tool of choice for evaluating residual mediastinal masses.