Anal squamous cell carcinoma (ASCC) is a rare cancer of the gastrointestinal tract, representing less than 5% of the digestive malignancies. The cytological and/or histological confirmation of a suspected lesion should be followed by a complete imaging evaluation to determine the extent of disease. We are presenting our experience with (18)F-FDG PET in ASCC. This is a retrospective case series of patients diagnosed and treated for ASCC at our institution(s). A total of 14 (18)F-FDG PET scans (8 for initial staging, 6 for evaluation of response to chemotherapy and radiation therapy) were performed in 8 patients (6 men, 2 women). The patients were 33-60 years old (average: 44+/-9). Our results showed that PET demonstrated the primary lesion at initial evaluation in 7 of 8 anal cancers and showed FDG- avid lymph nodes in 4 patients. Metastatic nodal involvement was confirmed by pathology in 2 patients; in the other 2 patients pathology showed reactive follicular hyperplasia. In another patient, follow-up PET demonstrated progression of disease despite treatment, prompting a change in disease management. In the remaining 5 patients with follow-up PET, the scans confirmed interval resolution of the (18)F-FDG uptake in the primary lesion, suggesting good treatment response. In conclusion, PET provides valuable diagnostic information in initial staging and evaluation of treatment response in ASCC that may significantly alter the clinical management. The emergence of the combined PET/CT scanner enhanced the accuracy of the imaging procedure in view of the precise anatomic localization of metabolic abnormalities.