OBJECTIVES: The aim of this prospective study was to assess the influence of different normalization procedures on relative changes in standardized uptake values (SUV) of F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the assessment of chemotherapy response in patients with colorectal carcinoma (CRC) and nonsmall cell lung carcinoma (NSCLC). METHODS: In 97 patients with CRC (n = 48) and NSCLC (n = 49), FDG-PET was performed before and during the course of chemotherapy. Relative changes in SUV (DeltaSUV) were determined after correction for injected dose and bodyweight, lean body mass, body surface area or a combination of bodyweight and plasma glucose. The predictive value for overall and progression-free survival with respect to the different normalized DeltaSUVs was assessed. RESULTS: In both CRC and NSCLC, no differences were seen in the degree of change between the four SUV-normalizations during chemotherapy. Cox regression analysis for overall survival showed significant hazard ratios of 1.14-1.16 per 10% SUV change in CRC and 1.10-1.13 in NSCLC and for progression-free survival hazard ratios of 1.15 per 10% DeltaSUV change in CRC and 1.10-1.12 in NSCLC. CONCLUSION: Relative changes in SUV is a strong predictor for survival in both CRC and NSCLC. None of the four normalization methods showed statistical advantage over the other. Therefore, simplifying the methods for analysis of FDG-PET data can improve the incorporation of FDG-PET in clinical treatment-response monitoring and may facilitate application in multicentre trials.