The aim of this study is to provide a simple means of estimating the total entropy of melting (DeltaS(m)(tot)) for a wide range of pharmaceutically and environmentally relevant organic compounds. A semiempirical equation based on only 2 molecular descriptors, the rotational symmetry number(sigma) and the molecular flexibility number (Phi), has been used to calculate DeltaS(m)(tot) for 1799 organic compounds. The average absolute error in estimating DeltaS(m)(tot) is 12.3 J/K(.)mol. This method gives entropy predictions that are comparable to those of a recently published group additivity method that utilizes 144 group contribution values.