The significance of positron emission tomography/computed tomography (PET/CT) in chronic lymphocytic leukemia (CLL) has not yet been systematically studied. This prospective study was aimed at assessing the benefit of PET/CT in patients with newly diagnosed or relapsed CLL and Richter transformation (RT). PET/CT examination was performed in 23 patients with newly diagnosed disease, 13 with relapsed disease and eight with suspected or histopathologically confirmed RT. In all patients, the maximum standardized uptake value (SUV(max)) was calculated. The median SUV(max) was 3.4 (range: 1.5-6.3) and 3.1 (range: 1.2-5.9) in newly diagnosed and relapsed patients, respectively. The median SUV(max) of patients with suspected or confirmed RT reached 16.5 (range: 7.2-25.3), a value different from that of the previous groups (p < 0.001). 2-[18F]fluoro- 2-deoxy-D-glucose ((18)F-FDG) PET/CT revealed inflammatory lesions in seven patients (16%) and synchronous tumors in two newly diagnosed patients. (18)F-FDG PET/CT may be a beneficial imaging method when used in individuals with CLL and suspected RT.