A matched molecular pair (MMP) analysis was used to examine the change in melting point (MP) between pairs of similar molecules in a set of approximate to 275k compounds. We found many cases in which the change in MP (MP) of compounds correlates with changes in functional groups. In line with the results of a previous study, correlations between MP and simple molecular descriptors, such as the number of hydrogen bond donors, were identified. In using a larger dataset, covering a wider chemical space and range of melting points, we observed that this method remains stable and scales well with larger datasets. This MMP-based method could find use as a simple privacy-preserving technique to analyze large proprietary databases and share findings between participating research groups.