The entropy of organic substances can be determined experimentally, using low-temperature calorimetry and the Third Law, by means of the equation Sexp0=∫T=0T0CpdT/T, where the subscript ‘exp’ indicates that the determination is experimental. The entropy of formation of such substances can be determined by means of the equation ΔfSexp0=Sexp0−∑Satoms0, where ∑Satoms0 represents the sum of the standard entropies of the individual atoms in a substance multiplied by their respective coefficients. However, experimental entropy determinations require very special equipment and are difficult to perform, so that at least for purposes of an initial estimate an empirical method for calculating values of entropy and entropy of formation has some advantages. Equations Scalc0=0.187∑Satoms0and ΔfScalc0=0.813∑Satoms0 can be used for this purpose, where the subscript ‘calc’ indicates that the values have been calculated empirically rather than determined experimentally. Using these latter values as the standards of comparison, it is shown that, for small molecular weight substances, the average value of Scalc0 is 2.03% greater than the average value of Sexp0, although the range is from 28.20 to −28.88%. For the same substances, the average value of ΔfScalc0 is 0.09% less than the average value of ΔfSexp0, with a range of 10.30 to −5.41%. For substances weighing >300Da, and for cells, the average value of Scalc0 is 0.04% less than the average value of Sexp0, with a range of 2.87 to −2.64%. The average value of ΔfScalc0 for these substances is 0.05% less than the average value of ΔfSexp0, with a range of 0.61 to −0.63%. For substances with molecular weights <300Da, the contributions of individual chemical groups on organic molecules can have a significant entropy effect. For substances with molecular weights greater than this, the entropy contributions of individual chemical groups on molecules appear to average out.