[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is increasingly used for response assessment in diffuse large B-cell lymphoma (DLBCL). A positive interim FDG-PET was shown to be associated with an unfavorable outcome in high-grade non-Hodgkin's lymphomas. For positive interim FDG-PET patients, the question of increasing the intensity of treatment using high-dose chemotherapy followed by auto-SCT (HDC-ASCT) remains unanswered. We retrospectively analyzed the prognostic value of FDG-PET in 42 DLBCL patients who were systematically evaluated at time of diagnosis, before and after HDC-ASCT. Of note, HDC-ASCT was part of the initial treatment strategy, while FDG-PET results did not influence the treatment approach. Results and outcome were analyzed according to FDG-PET results before and after HDC-ASCT. Patients were classified into three groups according to FDG-PET results before and after HDC-ASCT: those who were negative before and after (-/-; n=25), positive before and negative after (+/-; n=9) or positive before and after (+/+; n=8). The median follow-up was 34.5 (range, 19-74) months. The median EFS was significantly lower for the +/+ group (27.4 months) as compared with other groups (median not reached; P=0.0001). More importantly, there was no difference in term of EFS between the -/- group compared with the +/- group. These results suggest that HDC-ASCT can significantly improve the bad prognosis, otherwise indicated by a positive interim FDG-PET.