Non-small-cell lung cancer (NSCLC) is currently one of the most prevalent malignant tumors. It displays a wide variety of phenotypes which includes neuroendocrine markers commonly found on small-cell lung cancers (SCLC) such as the neural cell adhesion molecule (NCAM) and in particular its highly polysialylated isoform, embryonic NCAM (eNCAM). NSCLC with neuroendocrine differentiation may represent a subset of tumors whose cells have a more aggressive biological behavior. A tumor marker that distinguishes this latter sub-type could be of clinical relevance. Accordingly, we have raised a monoclonal antibody of the IgM type (JLP5B9) directed against capsular polysaccharides of N. meningitidis B which bears polysialic acid groups. We have demonstrated that JLP5B9 recognizes eNCAM with high affinity and that it is specifically directed against the polysialic acid moieties of NCAM. JLP5B9 was also found to react with human SCLC, NSCLC and neuroblastoma cell lines. We then used JLP5B9 as a specific probe for the detection of tissue eNCAM and found that it was expressed on up to 20% of tumor cells obtained from 5 out of 13 patients with NSCLC. This mAb deserves further investigation to evaluate its potential as a tool for serodiagnosis of lung cancer.