The entropy of organic substances can be determined experimentally, using low-temperature calorimetry and the Third Law, by means of the equation S-exp(0) = integral(T=0)(T0) C-p dT/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 Delta(f)S(exp)(0)= S-exp(0) - Sigma S-atoms(0) where Sigma S-atoms(0) 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 S-calc(0) = 0.187 Sigma S-atoms(0) and Delta(f)S(calc)(0) = 0.813 Sigma S-atoms(0) 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 S-calc(0) is 2.03% greater than the average value of S-exp(0), although the range is from 28.20 to -28.88%. For the same substances, the average value of Delta(f)S(calc)(0), is 0.09% less than the average value of Delta(f)S(exp)(0),, with a range of 10.30 to -5.41%. For substances weighing >300 Da, and for cells, the average value of S-calc(0), is 0.04% less than the average value of Delta(f)S(exp)(0) with a range of 2.87 to -2.64%. The average value of Delta(f)S(calc)(0) for these substances is 0.05% less than the average value of Delta(f)S(exp)(0), with a range of 0.61 to -0.63%. For substances with molecular weights <300 Da, 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.