The objective of this exploratory study was to evaluate the role of the insulin-like growth factor I receptor (IGF-IR) in esophageal adenocarcinoma (EADC). Using quantitative PCR, we studied IGF-IR mRNA expression in 52 well-characterized surgically resected EADC and matched histologically normal esophageal tissues, and examined IGF-IR expression levels in relation to clinicopathologic characteristics, body mass index (BMI), and the common IGF-IR polymorphism (G1013A), recently proposed to modify risk of obesity for EADC. Expression levels of IGF-IR mRNA were not significantly different between EADC and matched histologically normal esophageal epithelia. Although no significant associations were found between IGF-IR expression and BMI, tumor differentiation, stage or survival, when stratified by genotype, patients with the polymorphic A variant had significantly higher IGF-IR expression in EADC tissues compared with matched normal epithelia. These findings suggest that G1013A most likely modulates IGF-IR function, possibly by influencing gene transcription or mRNA stability, and represents a plausible mechanistic link underlying the association between obesity and esophageal malignancy.