We report a higher frequency of loss of heterozygosity at loci on the short arm of chromosome 3 in human epidermoid lung tumors than in other non-small cell lung tumors. This observation together with the already known involvement of the retinoids in the development of epidermoid metaplasia and neoplasia, especially in lung tissue, prompted us to investigate by RNAase protection assays the status of expression of a gene that maps on chromosome band 3p24 and codes for the B receptor for retinoic acid (RARB). We show that expression of RARB is detectable in normal lung tissue and in most of the cell lines derived from lung tumors, including the five non-small cell lines that clearly had a non-epidermoid phenotype. Strikingly, however, only one of the five epidermoid-tumor-derived cell lines studied showed detectable expression of RARB. Of two lines derived from adenosquamous tumors, one had a clear epidermoid differentiation, and this line also did not express RARB. Taken together, our results strongly implicate RARB in the evolution of epidermoid lung tumors.