AIM: The aim of this study was to assess the combined use of the radiotracers F-FDG and F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). PATIENTS AND METHODS: Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with F-FDG and F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). RESULTS: An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, F-FDG PET/CT-based treatment response revealed CR in 14 patients (F-FDG PET/CT CR), PR in 11 patients (F-FDG PET/CT PR) and progressive disease in four patients (F-FDG PET/CT PD). In terms of F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, F-NaF PET/CT depicted 56 of the 129 F-FDG positive lesions (43 %). Follow-up F-NaF PET/CT showed persistence of 81.5 % of the baseline F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to F-FDG negative. Treatment response according to F-NaF PET/CT revealed CR in one patient (F-NaF PET/CT CR), PR in five patients (F-NaF PET/CT PR), SD in 12 patients (F-NaF PET/CT SD), and PD in seven patients (F-NaF PET/CT PD). Dynamic F-FDG and F-NaF PET/CT studies showed that SUV, SUV, as well as the kinetic parameters K, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001). CONCLUSION: F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, F-NaF PET/CT does not seem to add significantly to F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.