Mutations in the winged-helix-nude (WHN) gene in the nude mouse and rat phenotypes lead to loss of hair and athymia. The human nude gene has recently been identified, but to date, its distribution in normal human tissues and thymus tumors has not yet been investigated. We used the RT-PCR technique for the detection of WHN transcripts in normal human organs and various mediastinal tumors, including various subtypes of thymic epithelial tumors. We could show that WHN is highly transcribed in the normal thymus and skin. Unexpectedly, few transcripts were also found in the normal kidney and thyroid gland. WHN mRNA could be detected in all thymoma subtypes (n = 14) and epidermoid thymic carcinomas as well as in all squamous cell carcinomas of the lung (n = 5) investigated, but was totally absent in all other mediastinal tumors (n = 11) lacking an epidermoid differentiation. We conclude that transcription of the human WHN is not strictly specific for human thymus and skin, but is also expressed, though at very low levels, in the normal human kidney and thyroid gland. In addition, WHN gene expression may identify not only thymomas but also epidermoid differentiation in mediastinal and pulmonary tumors.