We evaluated the clinical utility of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) on the precise localization of pathologic foci and exclusion of normal variants in the imaging evaluation of patients with esophageal carcinoma. Combined PET/CT scans were performed in 60 patients (50 males, 10 females, age range 47-84 years) with history of esophageal carcinoma either at the time of initial diagnosis (group I, n=14) or for surveillance and/or detection of recurrent and metastatic disease (group II, n=46). Prior treatments included esophagectomy with gastric pull-up (n=23), surgery and chemotherapy (n=3), surgery and chemoradiation therapy (n=10), chemotherapy alone (n=5), radiation therapy alone (n=2), and chemoradiation without surgery (n=3). Diagnostic validation was by tissue sampling in three patients and clinical/radiological follow-up for up to 1.5 years in the remaining patients. In group I, discordant abnormalities were noted in seven patients. PET demonstrated hypermetabolism in normal-size lymph nodes on CT in three patients that were considered likely true positive in view of concurrent existence of other adjacent enlarged hypermetabolic lymph nodes in the same nodal basin. Hypometabolic incidental CT abnormalities of up to 1-cm lung nodules were noted in three patients and pleural effusion in one patient, which were considered true negative in view of no change on follow-up PET/CT studies. In group II, both PET and CT showed concordant abnormalities in 23 patients. The precise image fusion of hypermetabolism in a liver lesion allowed a diagnostic CT-guided biopsy in one patient. PET demonstrated true positive hypermetabolic abnormalities in four patients that localized to structures, which were normal by noncontrast CT criteria, and true negative in one patient with hepatic fatty deposits. PET showed decline in metabolic activity of the primary lesion in one patient after chemotherapy, while the corresponding CT abnormality remained unchanged. PET/CT image fusion provided relevant complementary diagnostic information in 14 patients with discordant findings (23% of total) that resulted in biopsy in three cases, institution of chemotherapy in four cases, and a wait-and-watch strategy in seven cases. In conclusion, our findings add to the current body of literature that suggests that FDG-PET/CT scanning may improve the imaging evaluation of patients with esophageal cancer by providing complementary structural-metabolic information. In particular, our findings support the notion that PET/CT may be the most appropriate imaging modality in the evaluation of patients of esophageal cancer that may impact patient management.