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Analogously to Darwinian evolutionary theory, Skinner’s selectionist model explains behavioral evolution by appealing to variation and selection. The main purpose of this theoretical essay is to examine Skinner’s explanation of the origin and nature of variation. We draw parallels between the changes of conceptual framework (physicalism, vitalism, and Darwinism) used to explain variation in the history of biology and similar changes in the history of psychology (namely mechanicism, mentalism, and the model of selection by consequences). Our historical review highlights, on the one hand, the difficulties that Skinner faced regarding variation and, on the other hand, the different roles that variation has played in the development of his explanatory model.