Angiotrophic large cell lymphoma (ALCL) is a rare disease characterized by a proliferation of malignant lymphoid cells, usually of B-cell origin, within the lumina of small vessels and frequently involving the central nervous system (CNS). ALCL generally follows a rapidly fatal course and is rarely diagnosed prior to autopsy. Tumour cells are rarely present on examination of peripheral blood, cerebrospinal fluid (CSF) or bone marrow, therefore, an early diagnosis is heavily dependent on recognition of neurological manifestations which are present in over 80% of cases. A pre-mortem diagnosis of ALCL can be made in cases where brain biopsy has been performed. We report a case of a 45-year-old woman demonstrating clinical and laboratory features suggestive of multiple sclerosis associated transverse myelitis (MSA-TM) in whom ALCL was unexpectedly discovered at autopsy. Microscopic examination revealed diffuse CNS vascular involvement by neoplastic cells and prominent myelopathy of the upper thoracic spinal cord associated with ascending and descending tract degeneration of the spinal motor and sensory tracts. Neoplastic cells were immunoreactive for B-cell lymphoid markers. The present case is the first to demonstrate neoplastic B-cell clonality in ALCL using polymerase chain reaction (PCR) to detect abnormal V-D-J immunoglobulin gene rearrangements. ALCL should be considered in the differential diagnosis whenever a transverse myelitis is present in association with global encephalopathy and elevated serum lactate dehydrogenase. The neurological manifestations of ALCL with particular reference to its presentation as MSA-TM is discussed. Copyright 1999 Harcourt Publishers Ltd.