The preoperative staging of colorectal cancer (CRC) with (18)F-FDG PET is not as yet generally considered to be evidence based. We have found only 1 study that evaluated (18)F-FDG PET in a nonselected population with proven CRC. Several other studies have concentrated on more advanced disease. The aim of this study was to assess the potential clinical benefit of (18)F-FDG PET in the routine staging of CRC. Thirty-eight consecutive patients who had had CRC histologically proven by colonoscopy underwent prospective preoperative staging by plain chest radiography, sonography, CT, and (18)F-FDG PET. Sensitivity, specificity, and accuracy were retrospectively assessed by comparison with the histologic results after surgery (36 patients) or clinical follow-up (2 inoperable cases-both patients died within 1 y of the PET examination). The impact of (18)F-FDG PET on therapeutic decision making was evaluated by comparing medical records before and after (18)F-FDG PET. (18)F-FDG PET correctly detected 95% of primary tumors, whereas CT and sonography correctly detected only 49% and 14%, respectively. Lymph nodes were involved in 7 patients. The sensitivity, specificity, and accuracy of (18)F-FDG PET were 29%, 88%, and 75%, respectively. CT and sonography did not reveal any lymph node involvement. Liver metastases were present in 9 patients. (18)F-FDG PET, CT, and sonography had a sensitivity of 78%, 67%, and 25%, respectively; a specificity of 96%, 100%, and 100%, respectively; and an accuracy of 91%, 91%, and 81%, respectively. (18)F-FDG PET revealed further lesions in 11 patients. Levels of carcinoembryonic antigen and carbohydrate antigen 19-9 tumor markers were elevated in, respectively, only 33% and 8% of cases of proven CRC. (18)F-FDG PET changed the treatment modality for 8% and the range of surgery for 13% of patients. In total, (18)F-FDG PET changed the method of treatment for 16% of patients. Plain chest radiography and sonography did not bring any clinical benefits. No correlation was found between the level of tumor markers and the stage of disease. CT is necessary for confirmation of PET findings at extraabdominal sites (PET-guided CT) and for their morphologic specification at abdominal and pelvic sites before an operation. (18)F-FDG PET is the best method for the staging of CRC in all localities, despite the high rate of false-negative PET findings in patients with lymph node involvement. PET should be performed as a first examination after verification of CRC. We propose a PET/CT hybrid system as optimal in the staging of CRC.