Abstract Chemical imaging with high spatial resolution is one of the features of TOF-SIMS. However, degradation of the sample due to primary ion bombardment becomes problematic when the analysis area is small. Although polystyrene (PS) and polybutadiene (PB) separately show relatively distinct spectra, observation of their phase separation in PS/PB blends is difficult when the analysis area is small because degradation of both polymers and especially PS leads to disappearance of their characteristic peaks, resulting in low chemical image contrast. We therefore investigated the application of various forms of multivariate analysis (MVA) to the TOF-SIMS image data to improve the chemical image contrast. PCA, MCR, and the other forms of MVA provided improvement in contrast, but the images were still obscure and observation of phase separation remained difficult. Chemical derivatization using osmium tetroxide was also investigated, and found to give clear images of phase separation in the PS/PB blend. In quantitative determinations with MVA and chemical derivatization, PLS demonstrated the best predictive capability and chemical derivatization resulted in large deviations from both the bulk chemical composition and the determinations with MVA, particularly in regions of low PB content.