CD56 has been found to identify an isoform of the neural cell adhesion (NCAM). NCAM is a member of the immunoglobulin superfamily of cell adhesion molecules; it is related to a variety of leukocyte antigens and to several cell adhesion molecules believed relevant to malignant behavior in a variety of neoplasms. It contains polysialic acid, which appears to regulate binding avidity of NCAM and other cell adhesion processes. We have identified a group of NCAM-positive lymphomas. Compared to a group of NCAM-negative lymphomas, this group exhibited frequent involvement of unusual sites and a generally aggressive course. Another series of CD56-positive hematolymphoid malignancies has recently been described, from Hong Kong; this group also exhibited involvement of unusual sites and displayed a very aggressive course. Together these series suggest that NCAM on lymphoma is of biological and clinical significance in terms of tumor behavior and spread.