Siglec-6 also called CD327, one of the Sialic acid-binding immunoglobulin-like lectins (Siglecs) and type-1 transmembrane protein. Siglec-6 is predominantly expressed by mast cells, B cells, and a minor AS-type dendritic cell subset. Siglec-6 is an immune-inhibitory CD33-related Siglec and strongly binds to sialylated Tn-structures. As an exception, all Siglecs recognize the carboxyl group of sialic acid, but only Siglec-6 does not require the glycerol side-chain for binding. In cancer, Siglec-6 was recently found to be upregulated in circulating and urinary CD⁸⁺ T-cell of non–muscle-invasive bladder cancer patients, wherein a high level of Siglec-6 was associated with advanced bladder cancer. Additionally, Siglec-6 is prevalently expressed on acute myeloid leukemia blasts and transformed B cells in chronic lymphocytic leukemia. As Siglec-6 mRNA and protein are not expressed in hematopoietic stem cells, they are novel targets for CAR-T cell immunotherapy in chronic lymphocytic leukemia.