Gangliosides are glycosphingolipids expressed at the outer leaflet of the plasmatic membrane of cells from vertebrate organisms. These molecules exert diverse biological functions including modulation of the immune system responses. Aberrant expression of gangliosides has been demonstrated on malignant cells. Besides expression on tumor cell membranes, gangliosides are also shed in the tumor microenvironment and eventually circulate in patients blood. Gangliosides derived from tumors posses the capability to affect the immune system responses by altering the function of lymphocytes and antigen-presenting cells and promoting tumor growth. These molecules can be considered as tumor weapons directed to attack and destroy immunosurveillance mechanisms devoted to control cancer progression.