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BACKGROUND: The current gold standard for the surveillance of Barrett's esophagus is the Seattle four-quadrant biopsies protocol (4-QB). Using endoscopic brush cytology, this study prospectively investigated whether digital image cytometry (DICM) is of additional benefit over regular histology as a predictor for progression to high-grade dysplasia or cancer during a surveillance of at least 3 years. METHODS: The prospective cohort in this study included 93 patients (72% male) with Barrett's esophagus, baseline endoscopies, and at least one DICM in addition to 4-QB who had been followed up a minimum of 3 years at the time of analysis. High-grade dysplasia (HGD) and adenocarcinoma were defined as primary end points. The DICM was performed on Feulgen-restained cytology smears with a continuous collision detection (CCD) three-chip color video camera (Sony) and an AutoCyte QUIC DNA workstation. RESULTS: Of the 93 patients, 11 presented with the diagnosis of HGD and adenocarcinoma at baseline endoscopy. The remaining 82 patients were analyzed after a median follow-up time of 44 months (range, 36-65 months). Of these 82 patients, 9 (11%) had low-grade dysplasia (LGD) at baseline histology: One of two patients with LGD and aneuploid DICM showed HGD at follow-up assessment, whereas none of seven patients with LGD and diploid DICM had development of HGD. Of the 82 patients, 73 (89%) had either specialized intestinal metaplasia (SIM) without dyplasia or indefinite findings for dysplasia at baseline histology. Of the eight patients with SIM and intermediate/aneuploid DICM, two had development of HGD. None of those with negative or indefinite findings for dysplasia and diploid DICM had HGD at the follow-up evaluation. In summary, the three patients who had development of HGD showed a pathologic DICM at baseline, and no patient with diploid DICM had HGD. CONCLUSIONS: Cytometry from brush cytology as an add-on to histology appears to be of additional benefit during surveillance of Barrett's esophagus. Whereas an aneuploid/intermediate DICM warrants an early re-endoscopy, a diploid DICM underscores the low-risk status especially of patients with low-grade dysplasia.