BACKGROUND During follow‐up for patients with cervical carcinoma, elevation of serum squamous cell carcinoma antigen (SCC‐Ag) levels in the absence of detectable recurrent lesions presents a diagnostic and therapeutic challenge. In the current prospective study, the authors evaluated the use of fluorine‐18‐labeled fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) to detect disease recurrence in this setting. METHODS Women with cervical carcinoma who experienced complete responses to primary treatment or salvage therapy and who had no evidence of recurrent disease as detected by conventional methods but had serum SCC‐Ag levels ≥ 2.0 ng/mL on 2 consecutive occasions were eligible for the study. PET was performed within 2 weeks after the completion of conventional studies for the assessment of recurrence. RESULTS Twenty‐seven consecutive patients were registered for the current study. PET findings were positive for 19 patients: 14 who had a distant lesion or lesions, 2 who had a local lesion or lesions, and 3 who had both local and distant lesions. Of these 19 patients, 17 were confirmed to have recurrent disease; the remaining two were found to be free of disease but had severe anthracosis in the PET‐positive mediastinal lymph nodes. Seven of the eight patients with negative PET findings were not found to have recurrent disease on follow‐up. Overall, PET detected FDG‐avid lesions in 17 (94%; P < 0.001) of the 18 patients with recurrent disease. Seven of these 18 patients received therapy with curative intent; complete control was achieved in 6, four of whom currently are alive and free of disease. The addition of PET in the current setting curbed the use of futile curative therapy and significantly increased overall survival for patients in the current cohort compared with a historical group of 30 consecutive patients who had elevated SCC‐Ag levels as a first sign of recurrence. CONCLUSIONS PET expedited the detection of recurrent cervical carcinoma in patients with unexplained elevation of SCC‐Ag levels. Such expedited detection may have positive effects on patient survival. Cancer 2004. © 2004 American Cancer Society.