Aberrant lipid metabolism and altered plasma membrane composition are characteristics of cancerous cells affecting cell survival, proliferation and response to therapeutics. This process is driven by the dysregulation of lipid metabolism, including the key enzyme family lysophosphatidylcholine-acyltransferases (LPCATs), which synthesize phosphatidylcholine (PC) by adding specific fatty acids (FA) to lysophosphatidylcholine (LPC). Members of this family, namely LPCAT1 and 2 have preference for saturated FA, and therefore increase the overall saturation and stiffness of the membrane through their activity. Importantly, these enzymes are overexpressed in several kinds of cancer, including breast cancer where they have been linked to poor prognosis (LPCAT1) and drug resistance (LPCAT2). Here we aim to provide a chemical biology solution, in the form of new chemical tools and inhibitors, to characterize these enzymes, elucidate their role as cancer invasion drivers and exploit their potential as antineoplastic targets and biomarkers.