Fluoro-deoxyglucose positron emission tomography (FDG PET) enables the in vivo study of tissue metabolism, and thus is able to identify malignant tumours as hypermetabolic lesions by an increase in tracer uptake. Many papers have demonstrated both the relevant impact of FDG PET on staging of many cancers and the superior accuracy of the technique compared with conventional diagnostic methods for pre-treatment evaluation, therapy response evaluation and relapse identification. In particular PET was found useful in identifying lymph nodal and metastatic spread, thus altering patient management in more than 30% of cases. PET images, however, provide limited anatomical data, which in regions such as the head and neck, mediastinum and pelvic cavity is a significant drawback. The exact localization of lesions may also be difficult in some cases on the basis of PET images alone. The introduction of combined PET-computed tomography (PET-CT) scanners enables the almost simultaneous acquisition of transmission and emission images, thus obtaining optimal fusion images in a very short time. PET-CT fusion images enable lesions to be located, reducing false positive studies and increasing accuracy; the overall duration of the examination may also be reduced. On the basis of both literature data and our experience we established the clinical indications when PET-CT may be particularly useful, in comparison with PET alone. It should also be underlined that the use of PET-CT is almost mandatory for new tracers such as 11C-choline and 11C-methionine; these new tracers may be applied for studying tumours not assessable with FDG, such as prostate cancer. In conclusion PET-CT is at present the most advanced method for metabolic imaging, and is capable of precisely localizing and assessing tumours; fusion images reduce false positive and inconclusive studies, thus increasing diagnostic accuracy.