Using immunohistochemistry, we studied the overexpression of MDM2, p53, and NCAM proteins in human radiation-induced skin ulcers. We found that the positive rate of overexpression of MDM2, p53, and NCAM was 36%, 8%, and 32%, respectively. The overexpression of MDM2 protein was mainly observed in the nuclei of fibroblasts in the deeper part of the ulcer; that of p53 protein was in the nuclei of the epidermis and in the cytoplasm of fibroblasts and endothelial cells, whereas that of NCAM was located in the cytoplasm of squamous epithelial cells of the epidermis and in fibroblasts, fibrocytes, endothelial cells, and leiomyocytes in the media of arteriolar walls. The overexpression of MDM2, p53, and NCAM may be related to the poor healing of radiation-induced skin ulcers and the cancer transformation.