CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These cancers include renal cancer, prostate and bladder cancers, acute leukaemias, hepatocellular carcinoma, breast cancer and melanoma. The biological role of CD15 is interaction with E-, L- and P-selectins (adhesion molecules), allowing for adhesion with endothelial cells. In this way, cancer cells start to interact with the endothelia of blood vessels and consequently move out from the blood flow to the surrounding tissues. Blockage of the antigen’s function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibody-based therapies. CD15 may serve as a prognostic marker for patients and there are high hopes for its use in the immunotherapeutic treatment of tumours. CD15s is a sialyl derivative of CD15 that possesses its own unique characteristics. Its soluble form may act as a competitive inhibitor of the interaction of cancer cells with epithelial cells and thus disallow migration through the vessels. However, the prognostic relevance of CD15 and CD15s expression is very complex. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews its significance for clinical applications.