The incidence of human esophageal squamous cell carcinoma in males is well-known to be higher than in females and its biological action in male patients is generally much more aggressive than that of the female. Recently, aberrations and/or other abnormalities of the sex chromosomes, especially the Y chromosome, have been postulated to be involved in some of the differences in the incidence and/or biological action of human malignancies between male and female patients. Therefore, in this study, we examined abnormalities of the sex chromosomes in cell smears obtained from 30 male patients diagnosed with esophageal squamous cell carcinoma. In addition, TE series cell lines, derived from esophageal squamous cell carcinomas, were studied for sex chromosome abnormalities by utilizing a simultaneous double color fluorescent in situ hybridization (FISH) and these findings were correlated with various clinicopathological parameters in order to examine its likely biological significance. In esophageal squamous cell carcinoma, Y chromosome loss was detected in all cases studied (1.6-86.9%, mean 22.98 +/- 22.04%), but the loss of the X chromosome was encountered in only 6 of the cases (7.1-40.6%, mean 15.90 +/- 12.46%). There was no significant association between the rate of Y chromosome loss in carcinoma cells and any of the clinicopathological parameters examined including age and stage of the cancer. Loss of the Y chromosome was observed in only two cases of adjacent non-pathological esophageal squamous cell epithelium. Among the TE series examined, the cell lines derived from male patients demonstrated loss of the Y chromosome in all cell lines (1.4-92.9%, mean 44.92 +/- 42.55%), but the great majority of cell lines derived from female patients were associated with the karyotype of XX. These results indicated that the loss of the Y chromosome is associated with the malignant phenotype in human esophageal squamous epithelium, but possibly not with biological behavior. These results also suggested that at least one X chromosome is indispensable for the survival of esophageal squamous cell carcinoma.