A key challenge for molecular cancer diagnostics is the identification of appropriate biomarkers and detection modalities. One target of interest is the cell surface, which is involved in important steps of cancerogenesis. Here, we explore the feasibility of a label-free spectroscopic profiling of the cell surface chemistry for the detection of tumor cells. Vibrational spectra of the cellular surfaces of tumor and nontumor breast and prostate cell lines were recorded on silver nanoparticle substrates using surface-enhanced Raman spectroscopy (SERS). The quantitative analysis of the spectra revealed characteristic differences, especially in the spectral range between 600 and 900 cm<sup>−1</sup>. The detection of tumor-cell-specific differences in the recorded SERS spectra indicates the possibility of improving the precision of current cancer detection and staging approaches through a spectroscopic profiling of cell surface cancer biomarkers