We provide data which suggest that the SHH and WNT pathways may be epigenetically involved in BCC pathobiology, since both networks are affected by aberrant promoter methylation of SHH, APC and SFRP5. Aberrant methylation and associated gene silencing of APC and SFRP5 may contribute to the pathogenesis of BCC by impairing negative regulation of WNT pathway activity. This evidence concerns the gene SHH and skin basal cell carcinoma.