Studies have shown that the accuracy of Random Forest (RF)-based Scoring Functions (SFs), such as RF-Score-v3, increases with more training samples, whereas that of classical SFs, such as X-Score, does not. Nevertheless, the impact of the similarity between training and test samples on this matter has not been studied in a systematic manner. It is therefore unclear how these SFs would perform when only trained on protein-ligand complexes that are highly dissimilar or highly similar to the test set. It is also unclear whether SFs based on machine learning algorithms other than RF can also improve accuracy with increasing training set size and to what extent they learn from dissimilar or similar training complexes.