18F-fluorodeoxyglucose positron emission tomography (18FDG PET) has become an essential technique in oncology. Accurate segmentation and uptake quantification are crucial in order to enable objective follow-up, the optimization of radiotherapy planning, and therapeutic evaluation. We have designed and evaluated a new, nearly automatic and operator-independent segmentation approach. This incorporated possibility theory, in order to take into account the uncertainty and inaccuracy inherent in the image. The approach remained independent of PET facilities since it did not require any preliminary calibration. Good results were obtained from phantom images [percent error =18.38% (mean) ± 9.72% (standard deviation)]. Results on simulated and anatomopathological data sets were quantified using different similarity measures and showed the method was efficient (simulated images: Dice index =82.18% ± 13.53% for SUV =2.5 ). The approach could, therefore, be an efficient and robust tool for uptake volume segmentation, and lead to new indicators for measuring volume of interest activity.