The incidence of esophageal carcinoma continues to increase whilst its prognosis remains poor. The most dramatic reduction in mortality is likely to follow early diagnosis of the preinvasive precursor lesion, Barrett's esophagus (BE), coupled with treatment of dysplastic lesions. The major risk factor for BE is gastroesophageal reflux disease, however this is highly prevalent and only a small proportion of individuals have BE, therefore an endoscopy-based screening strategy to detect BE is unfeasible. Minimally invasive esophageal sampling devices offer an alternative, cost-effective strategy which can be deployed within an at-risk population in a primary care setting to identify individuals with probable BE who can then be referred for endoscopic confirmation. The device that has currently progressed furthest in clinical trials is the CytospongeTM which collects cells from the gastric cardia, gastroesophageal junction and along the whole esophageal length. The cell sample is processed into a formalin-fixed paraffin-embedded block and sections assessed for the presence of intestinal metaplasia. TFF3 immunohistochemistry has consistently been shown to be a valuable adjunct that increases the accuracy of the CytospongeTM test by highlighting early goblet cells which may be missed on morphological assessment and by allowing pseudogoblet cells to be differentiated from true goblet cells.