Desmosomal cadherins in humans involve three isoforms, each in two splicing variants, of desmocollin (DSC1-3) and four isoforms of desmoglein (DSG1-4). DSGs are transmembranous desmosomal adhesive glycoproteins, which are generally expressed in a differentiation-specific manner. The aim of this study was to measure intensities of expression of both DSG2 and DSG3 in basal cell carcinoma (BCC) and to compare them with those in normal epidermis. Using immunoperoxidase staining on frozen tissue with monoclonal antibodies against human DSG2 and DSG3, DSG2 and DSG3 expression was assessed in specimens from 26 BCC patients. There was a significant overexpression of DSG2 and a significantly lower expression of DSG3 in BCC tumor nests (BCCpos) compared to non-BCC-affected epidermis (BCCneg). There was no significant correlation between the intensities of DSG2 and DSG3 expression in BCCpos, but there was a significant correlation (r=+0.6092) between these markers in BCCneg. That loss of coordination of DSG2 and DSG3 expression in BCC, revealed with quantitative digital morphometry, might explain in part the BCC behavior as a locally invasive tumor. Our study further suggests that in human skin, DSG2-mediated adhesion appears to be more proliferation-associated, whereas DSG3-mediated adhesion seemingly is more differentiation-associated.