An office based non-invasive screening test for detection of Barrett's esophagus (BE) is disclosed. Over expression of specific molecular target molecules is used for the diagnosis of BE. In certain embodiments, the molecular targets are detected by quantitative reverse transcriptase PCR (RT-qPCR). In certain embodiments, a diagnostic test is provided that includes collection of esophageal brushings and testing for expression of one or more of MUC2 and CDX2, wherein expression of MUC2 and/or CDX2 in the esophagus is diagnostic for Barrett's esophagus. In certain embodiments, the diagnostic test may also utilize and immunoassay to determine MUC2 protein concentrations to establish the diagnosis of Barrett's esophagus.