We examined the role of fluorodeoxyglucose-positron emission tomography (FDG-PET) and the addition of involved field radiotherapy (IFRT) as potential modifiers of salvage therapy. From January 2000 to June 2007, 83 patients with chemosensitive relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) underwent FDG-PET scans following second-line chemotherapy before high-dose therapy with autologous stem cell rescue (HDT/ASCR). We evaluated the prognostic value of having a negative FDG-PET scan before HDT/ASCR and whether IFRT improved the outcomes. Median follow-up was 45 months, and the 3-year PFS, disease-specific survival (DSS) and OS were 72, 80 and 78%, respectively. Multivariate analysis revealed that a positive FDG-PET scan had worse PFS (hazard ratio=(HR) 3.4; P=0.014), DSS (HR=7.7; P=0.001) and OS (HR=5.4; P=0.001), and that patients not receiving IFRT had worse PFS (HR=2.7; P=0.03) and DSS (HR=2.8, P=0.059). Patients who received IFRT had better local control with fewer relapses within prior involved sites compared with those that did not receive IFRT (P=0.006). These outcomes confirm the important prognostic value of FDG-PET scans before undergoing HDT/ASCR. It also suggests that the role of IFRT should be evaluated further.