Modern high-resolution mass spectrometry provides the great potential to analyze exact masses of thousands of molecules in one run. In addition, the high instrumental mass accuracy allows for high-precision formula assignments narrowing down tremendously the chemical space of unknown compounds. The adequate values for a mass accuracy are normally achieved by a proper calibration procedure that usually implies using known internal or external standards. This approach might not always be sufficient in cases when systematic error is highly prevalent. Therefore, additional recalibration steps are required. In this work, the concept of mass difference maps (MDiMs) is introduced with a focus on the visualization and investigation of all the pairwise differences between considered masses. Given an adequate reference list of sufficient size, MDiMs can facilitate the detection of a systematic error component. Such a property can be potentially applied for spectral recalibration. Consequently, a novel approach to describe the process of the correction of experimentally derived masses is presented. The method is based on the estimation of the density of data points on MDiMs using Gaussian kernels followed by a curve fitting with an adapted version of the particle swarm optimization algorithm. The described recalibration procedure is examined on simulated as well as real mass spectrometric data. For the latter case, blood plasma samples were analyzed by Fourier transform ion cyclotron resonance mass spectrometry. Nevertheless, due to its inherent flexibility, the method can be easily extended to other low- and high-resolution platforms and/or sample types.