Twenty-seven formalin-fixed, paraffin-embedded skin samples were examined to determine the usefulness of the loss of beta-2-microglobulin (B2m) in determining the malignancy of the epithelial cells of skin tumors. Our results confirm that there is loss of B2m from the cell surface in certain malignant lesions whereas the cells in the clearly benign lesions retain B2m on their cell membrane. Variable staining in the low-grade malignant and premalignant lesions renders B2m as an unreliable cell surface marker for differentiating borderline lesions.