ICAM–1 (intercellular adhesion molecule 1) and MPZ (myelin protein zero) are thought to be a factor in the integrity of nerve tissues. In this report, we attempted to trace the expression of ICAM–1, responsible for cell-to-cell adhesion, and of MPZ, the main constituent of myelin sheath, in malignant tissues of the sciatic nerve (SN) in inbred male Copenhagen rats. AT–1 Cells (anaplastic tumor 1) were injected in the perineurial sheath, and tissues of the SNs were collected after 7, 14 and 21 days and compared to a sham-operated group of rats (n = 6 each). Tissues were sectioned and histologically examined, under light microscope, and stained for measuring the immunoreactivity of ICAM–1 and MPZ under laser scanning microscope. The cancer model was established, and the tumor growth was confirmed. ICAM–1 showed severe decreases, proportional to the growing anaplastic cells, as compared to the sham group. MPZ revealed, however, a distinct defensive pattern before substantially decreasing in a comparison with sham. These results support the notion that malignancies damage peripheral nerves and cause severe axonal injury and loss of neuronal integrity, and clearly define the role of ICAM–1 and MPZ in safeguarding the nerve tissues.