Chromosomal band 1q21 contains a number of genes, constituting the Epidermal differentiation complex (EDC), most of which are involved in the process of terminal differentiation of the human epidermis and implicated in several disorders of keratinization and cancer. The physical map of 1q21 has been refined by generating 400 YAC derivatives. These products have allowed us to localize EDC genes and additional ESTs precisely. The transcriptional map of the region has been extended by positioning 20 ESTs reported to map between D1S442 and D1S305. Eight of the ESTs are localized in two distinct clusters, confirmed by isolating PACs and chromosome 1-specific cosmids. Two of the ESTs correspond to the genes for YL1 and selenium-binding protein, both of which have potential tumor suppressor activity. Through the use of fragmented YACs and bacterial clones, the order of markers and ESTs in the region has been established as follows: cen-A002O32-Bda44g03-Cda10d12-Bdab5d06, H60056, A005K39-D1S442-WI5663-WI7969-Cx40-Cda0g e12-Cda0kh05-A002D26- A008S07-Cda0ff08-D1S498-S100A10-WI7815( THH)-WI7217(FLG)-D1S1664-INV-SPRR2A- LOR-A001X21-D1S305-tel.