In order to estimate the size of an initial population of nucleic acids in a sample of interest, in particular by PCR, the following steps are performed: a) providing a model of the effectiveness (En) of the PCR, the model comprising a constant stage (E0) followed by a non-constant stage, the stages being united by a changeover region having a changeover index (CEEP); b) using the model of effectiveness to express a relationship between the changeover index and a parameter representative of the initial population size; and c) determining the changeover index by comparison with the experimental measurements, and deducing therefrom the initial population size in the sample of interest.