In recent years a number of studies have been published showing strong value of positron emission tomography using 18-Fluorine 2-fluoro-deoxy-D-glucose (FDG-PET) in term of diagnosis, response to treatment, disease recurrence and prognostic indicator in early restaging. This study observed 17 patients who presented contemporary disease progression in some localizations as well as regression in others (PROG + REG pattern); this investigation assessed that this unusual pattern of FDG uptake lead to an unfavorable prognosis. Among 1280 FDG-PET scans performed between August 2003 and December 2004 on patients affected by lymphoma with suspected recurrence, attention was focused on 17 patients presenting a PROG + REG pattern. At follow-up (4 months) only 1/17 (6%) patient was in complete remission after salvage therapy, while 6/17 (35%) had stable disease and 10/17 (59%) had rapid progression of the disease. This study further strengthens the role of FDG-PET in lymphoma patients follow-up, as it can provide useful information to better differentiate those cases who may benefit from conventional treatments from others in whom additional treatment would provide avoidable toxicity.