Acidic mucin-positive nongoblet columnar cells (NGCC) have recently been observed in the surface epithelium of the gastroesophageal junction (GEJ) and distal esophagus in resections from patients with traditional long segment (>3 cm) Barrett's esophagus (BE). However, the significance of finding acidic mucin-positive NGCC in the surface epithelium of biopsy specimens from the distal esophagus/GEJ region in the absence of goblet cells (GC) remains unknown. Therefore, to determine the significance of mucin histochemical changes in the distal esophagus/GEJ region, we analyzed and compared the types, prevalence, and distribution of neutral and acidic mucins in biopsy specimens obtained from 2 groups of patients: those with (32 patients) and those without (107 patients) GC identified in this area. Various mucin histochemical stains (PAS-Ab pH 2.5, HID-Ab pH 2.5, PB/KOH/PAS) were used to identify neutral mucins, acidic mucins (sialomucins and sulphomucins), and o-acetylated sialomucins. The results were compared between the 2 patient groups and correlated with the clinical, endoscopic, and pathologic features. Compared with patients without GC, patients with GC had a significantly higher male/female ratio and a higher proportion of patients with greater than 3 cm of columnar epithelium within the esophagus. Acidic mucin (sialomucin and sulphomucin)-positive NGCC in the surface, foveolar, and glandular epithelium did not show any correlation with any of the clinical, endoscopic, or pathologic features, such as esophagitis, carditis, antritis, Helicobacter pylori infection, or length of columnar epithelium in the distal esophagus. However, acidic mucin-positive NGCC correlated strongly with the presence of GC (P < .001). For example, sialomucin-positive NGCC were present in 28 of 32 (88%) patients with GC compared with 31 of 107 (29%) patients without GC (P < .001). Similarly, sulphomucin-positive NGCC were present in 20 of 32 (62%) patients with GC, compared with 11 of 107 (10%) patients without GC (P < .001). Of the non-GC cases, all biopsy specimens that stained positively for sulphomucin in surface NGCC (11 specimens), except one, showed staining restricted to the surface of multilayered epithelium, a distinctive type of epithelium that shows morphological, ultrastructural, and cytochemical features of both squamous and columnar epithelium. Sialomucin positivity in surface NGCC from the distal esophagus/GEJ region is a sensitive (sensitivity 88%), but nonspecific (specificity 71%), indicator of GC metaplasia. In contrast, sulphomucin expression in NGCC from the same anatomic area is a less sensitive (sensitivity 62%), but more specific (specificity = 90%) marker for the presence of metaplastic epithelium, of either the GC or the multilayered epithelial cell type and thus may represent an early or incomplete form of intestinal metaplasia.