This review highlights and discusses our current knowledge of the SphK aberrant signaling that may contribute or drive SphK-coupled oncogenicity with particular interest directed towards the current understanding of SphK isozymes, alternatively spliced isoforms “dicing and splicing” and the potential contribution of these isoforms to cancer cell biology and their influence on SphK/S1P based cancer therapeutics. Here, SPHK1 is linked to cancer.