Abstract: Methods for diagnosing an upper gastrointestinal (GI) cancer in a subject by determining an amount of one or more biomarkers in a biological sample from the subject are provided. Methods for determining whether to initiate or continue prophylaxis or treatment of an upper GI cancer in a subject by determining any measurable change in the amounts of the at least one biomarker in each of a series of biological samples provided over a time period are also provided.