There is renewed interest in chromoendoscopy, which is an old endoscopic technique first described more than two decades ago. It seems promising for improving detection of severe dysplasia and cancer of the esophagus. Staining with Lugol's solution is effective in detecting high-grade dysplasia and early squamous cancers of the esophagus, particularly in high-risk patients with head and neck cancers who may have synchronous esophageal tumors. It can also help delineate squamous from columnar metaplastic epithelium in patients with suspected Barrett's esophagus. Methylene blue selectively stains specialized columnar epithelium and may help diagnose short segment Barrett's esophagus. It may also direct biopsies to endoscopically inapparent high-grade dysplastic or malignant mucosa due to differential staining of dysplastic and nondysplastic tissue. In prospective studies involving patients and esophagectomy specimens, absent to light blue staining and heterogeneous staining pattern were significantly associated with high-grade dysplasia and/or adenocarcinoma. Biopsies from these areas led to detection of low grade dysplasia (five patients), high grade dysplasia (one patient), and adenocarcinoma (one patient) that were missed by random biopsy in a randomized sequential trial. When compared with 4-quadrant, jumbo random biopsy, methylene blue directed biopsy was significantly better in diagnosing intestinal metaplasia (Barrett's esophagus) and dysplasia, using fewer biopsies per patient. This led to a decrease in the overall and mean surveillance cost and the cost per cancer diagnosed. Chromoendoscopy is a simple, inexpensive, readily available endoscopic technique that may improve the diagnosis of esophageal cancer.