Evidence indicates that blood group-related Lewis (Le) antigens (glycosphingolipids: GSLs and Glycoproteins: GPs) are tumor-associated cell surface molecules. The Lea, Leb, LeX, LeY, and their sialosyl-derivatives, all N-acetylglucosaminyl-containing glycoconjugate antigens, are overexpressed on the surfaces of breast, colon, and ovarian cancer cells during metastasis. A few inhibitors of GSLs (l-/d-PPMP) and DNA (cisplatin) biosynthesis, betulinic acid (a herbal origin of a triterpenoid used for cancer treatment in China), melphalan, and disialosylgangliosides (GD3 and GD1b) induced apoptosis (intrinsic mitochondrial or extrinsic receptor-mediated pathways) in human breast (SKBR-3, MCF-7, and MDA-468) and colon (Colo-205) cells. These chemicals are suggested to be potential anticancer drugs. In this review, we try to compare our recent observations with reported observations from many other laboratories. We discuss the induction of apoptosis in breast and other cancer cells by various new chemicals. We also discuss the biosynthesis and regulation of GSLs in nonapoptotic and apoptotic cancer cells.