Raman spectroscopy is widely used for study of lipids and membrane models. A severe limitation of this technique lies in the low Raman cross section requiring high sample concentrations. We report sensitive detection of synthetic 1,2-dimyristoyl-3-trimethylammonium-propane (DMTAP) lipid employing two Raman techniques with improved sensitivity: drop coating deposition Raman (DCDR) and surface-enhanced Raman scattering (SERS) spectroscopies. DCDR provided well-reproducible DMTAP spectra without considerable loss of its solution properties if measured from the ‘coffee ring’ pattern of a drop dried on a SpectRIMTM plate. DMTAP was detected at ~10 μM initial solution concentration, which is about three orders of magnitude lower than that for conventional Raman spectroscopy. Moreover, SERS spectra from dried ring of Ag hydrosol/DMTAP system were obtained down to ~0.3 μM DMTAP concentration, which means that sensitivity of SERS is about five orders of magnitude higher than that of conventional Raman spectroscopy. In contrast to the DCDR technique, good SERS spectra of DMTAP were obtained only from some spots of the ring containing big nanoparticle aggregates, and the structural properties of DMTAP were significantly perturbed by adsorption on the Ag nanoparticles. Copyright © 2013 John Wiley & Sons, Ltd.