A systematic investigation to assess the degree of similarity between polymorphs was carried out. A similarity indices (IX) approach was applied in ten series of polymorphs with different characteristics and number of molecules in the asymmetric unit. Geometric (ID), contact area (IC), and stabilization energy (IG) parameters were used. It was possible to situate each comparison in different regions of similarity within the polymorphism phenomenon and determine the boundaries between quasi-isostructural polymorphs and polymorphs of low similarity. The multiparameter IDCG index was used as a robust tool to determine the total similarity within the polymorphism phenomenon. The highest contribution of the stabilization energy parameter (45%) toward the final value of similarity (IDCG) was observed, followed by the contact area index (32%). The geometric index contributed approximately 23% to the final value of IDCG. This information reinforces the importance of the contact area and stabilization energy in assessing the degree of similarity between crystalline structures. A new descriptor (IQ) based on the comparison of the energetic contribution of intermolecular interaction types present in each crystal structure is presented. IQ can be a versatile tool and applicable even for systems that do not share any similarity.