Chronic myelitis from Whipple's disease of the spinal cord is extremely rare. The differential diagnosis includes chronic inflammatory lesions, viral or bacterial infections, and tumours of the spinal cord. Here we present a 50-year-old man with mild sensory deficits because of a large lesion of the cervical spinal cord who markedly showed improvement during probatory antibiotic therapy. PCR and jejunal biopsy were initially negative and only later confirmed the diagnosis of Whipple's disease. Clinical and neuroradiological criteria are suggested which may be of help in the early diagnosis of spinal Whipple's disease before confirmation by molecular biology or histology.