The most important differential diagnosis of specialized intestinal columnar cell metaplasia (Barrett's-mucosa) is the intestinal metaplasia of the cardia mucosa (possibly caused by Helicobacter infection). Furthermore it happens from time to time that Barrett's regenerative epithelium is overdiagnosed as low-grade dysplasia (unequivocal intraepithelial neoplasia). This might explain the disappearance of many low-grade dysplasias during further follow-up. Mucosal adenocarcinomas are often underdiagnosed as dysplastic lesions. Therefore many authors tried to establish molecular methods for improvement of the diagnostic possibilities. Immunohistochemistry or PCR with p53 and HER 2-neu might give at least some help but a negative reaction does not exclude a neoplasia in every case. The gold standard is careful endoscopy and biopsy taking with good documentation of the endoscopical findings and most important still the routine H&E stain are the only reliable diagnostic tools.