Overprediction is a major limitation of current crystal structure prediction (CSP) methods. It is difficult to determine whether computer-predicted polymorphic structures are artefacts of the calculation model or are polymorphs that have not yet been found. Here, we reported the well-known vitamin nicotinamide (NIC) to be a highly polymorphic compound with nine solved single-crystal structures determined by performing melt crystallization. A CSP calculation successfully identifies all six Z′?=?1 and 2 experimental structures, five of which defy 66 years of attempts at being explored using solution crystallization. Our study demonstrates that when combined with our strategy for cultivating single crystals from melt microdroplets, melt crystallization has turned out to be an efficient tool for exploring polymorphic landscapes to better understand polymorphic crystallization and to more effectively test the accuracy of theoretical predictions, especially in regions inaccessible by solution crystallization.