The ability of randomly obtained biopsy specimens to identify intestinal metaplasia in the distal esophagus is low. Use of vital staining has been suggested, as stains are taken up by areas histologically identified as specialized intestinal metaplasia (SIM). This study evaluated the role of methylene blue (MB) staining for identification of SIM in GERD patients undergoing a screening endoscopy. Chromoendoscopy of the distal esophagus using 1% MB was performed on 52 GERD patients presenting for their first endoscopy. Biopsies were obtained from areas that were stained darkly, stained lightly, unstained, or macroscopically abnormal. In patients with no MB staining, four-quadrant biopsy of the distal esophagus was performed. Twenty-seven patients (52%) showed staining with MB, while 25 patients did not. Two hundred sixty-six biopsies were obtained. SIM was detected in 11 (21%) subjects (SIM+) but not in the remaining 41 (SIM-). One hundred sixty-five biopsies were unstained (25 SIM+, 140 SIM-) and 101 were stained (12 SIM+, 89 SIM-). The per-biopsy sensitivity and specificity of MB for detection of SIM were 32.4 and 85%, while the per-patient sensitivity and specificity were 63.3 and 51.2%. MB staining for detection of SIM in GERD patients without a macroscopic appearance suggestive of a columnar-lined esophagus is a poor screening tool for SIM.