Objective: To assess the potential role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in patients with unexplained rising carcinoembryonic antigen (CEA) levels after the treatment of colorectal cancer. Background: A rising CEA level after the resection of colorectal cancer is an early indicator of tumor recurrence. However, conventional imaging techniques have limited sensitivity for detecting recurrent disease in such patients. Especially after surgical intervention, FDG-PET is rapidly gaining an important role in establishing the extent of disease in the oncology patient. Methods: Twenty-two patients with abnormal CEA levels and normal results of conventional methods of tumor detection were studied with FDG-PET. The PET results were compared with pathologic findings (n = 9) and long-term radiologic and clinical follow-up (n = 13). Results: FDG-PET was abnormal in 17 of 22 patients. Tissue sampling was available in 7 of these 17 patients; all of these had recurrent disease. Definitive curative surgical intervention was performed in four patients. Subsequent dedicated imaging findings and clinical course confirmed the presence of extensive disease in 8 of the remaining 10 patients; the PET results in the other 2 patients were considered falsely positive. FDG-PET was negative in 5 of 22 patients. No disease was found by tissue sampling (n = 2) and clinical follow-up (n = 3). Overall, the positive-predictive value for PET was 89%, (15 of 17) and the negative-predictive value was 100% (5 of 5). Conclusions: When conventional examinations are normal, FDG-PET is a valuable imaging tool in patients who have a rising CEA level after colorectal surgery.