A 29-year-old man was examined for disseminated erythematous scaling patches and plaques and reddish, partially ulcerated nodules. Histological examination showed a dense, diffuse, epidermotropic infiltrate located in the entire dermis to the subcutaneous tissue, composed mainly of large pleomorphic T lymphocytes. Immunohistochemistry revealed positivity of neoplastic cells for T-cell-associated markers, negativity for CD30 antigen and for B-cell markers. Polymerase chain reaction analysis detected a clonal amplification of T-cell receptor gamma. Based on clinicopathological and molecular findings, the diagnosis of large T-cell lymphoma (LCL) arising from a pre-existing mycosis fungoides was made. Seven months after primary diagnosis, meningeal and peripheral nervous system involvement developed with no other evidence of systemic disease. Despite chemotherapy and radiation therapy, the patient died 3 months after the diagnosis of nervous system involvement. In patients with cutaneous LCL, mild neurological symptoms may precede the complete diagnostic picture by some weeks. A rapid and fatal progression characterizes the clinical course of the disease.