A 68-year old man experienced a progressive proximal tetraparesis with anhidrosis and a single episode of horizontal diplopia before presenting exertional dyspnea; pulmonary investigations revealed a small cell carcinoma of the lung. Clinical and electrophysiological investigations with abnormal SFEMG, repetitive stimulations and autonomic assessment pointed to a pre-synaptic neuromuscular dysfunction compatible with a Lambert-Eaton syndrome. Antibodies to acetylcholine receptors and calcium channels were negative. Thoracic radiotherapy combined with chemotherapy produced marked improvement: repeated electrophysiological evaluations showed a strong correlation between median nerve CMAP amplitude and clinical course. This case prompted us to discuss current concepts of pre-synaptic dysfunction, and paraneoplastic syndrome, and to review therapeutic strategies, in the light of recent studies of Lambert-Eaton syndrome.