Researchers are often interested in comparing statistical network models estimated from groups that are defined by the sum-score of the modeled variables. A prominent example is an analysis that compares networks of individuals with and without a diagnosis of a certain disorder. Recently, several authors suggested that this practice may lead to invalid inferences by introducing Berkson’s bias. In this article, we show that whether bias is present or not depends on which research question one aims to answer. We review five possible research questions one may have in mind when separately estimating network models in groups that are based on sum-scores. For each research question, we provide an illustration with a simulated bivariate example and discuss the nature of the bias, if present. We show that if one is indeed interested in the network models of the groups defined by the sum-score, no bias is introduced. However, if one is interested in differences across groups defined by a variable other than the sum-score, detecting population heterogeneity, the network model in the general population, or inferring causal relations, then bias will be introduced in most situations. Finally, we discuss for each research question how bias can be avoided.