Desmoplakin II (DPII) is a new marker for identification of epithelium and epithelial tumors. Expression of DPII in 217 tumors cases was studied immunohistochemically by ABC method using an anti-DPII monoclonal antibody which reacts with tissue on formalin-fixed, paraffin-embedded sections. A monoclonal antibody against cytokeratin (CK) was employed to compare with the antibody. Immunohistochemical staining showed that 147 of the 163 epithelial tumors and bi-directional differentiation tumors expressed DPII (90.7%); 92 of the 163 tumors expressed CK (56.4%); 54 tumors lacking desmosome expressed neither DPII nor CK. All CK positive staining was located in cytoplasm while most DPII positive dotty staining was located at the cell-cell borders, some DPII staining was present in cytoplasm. These results demonstrate that the anti-DPII monoclonal antibody is a useful immunohistochemical probe for identification of desmosome-containing tumors. Antibodies against other epithelial markers such as keratin should be employed together with anti-DPII monoclonal antibody when differentiation is made between epithelial and non-epithelial tumors.