The present functional magnetic resonance imaging (fMRI) study investigates modifications of brain activation patterns related to the training of two different arithmetic operations, multiplication and subtraction. Healthy young adults were trained in five sessions to answer multiplication and subtraction problems. In the following fMRI session, trained and new untrained problems closely matched for difficulty were presented in blocked order. Contrasts between untrained and trained operations showed stronger activation of inferior frontal and parietal regions, especially along the banks of the intraparietal sulcus. The reverse contrasts, trained minus untrained operations, yielded significantly higher activation in the left angular gyrus for multiplication but no significantly activated area for subtraction. This suggests that training leads to a reduction of general purpose processes, such as working memory and executive control in both operations, indicated by the decrease of activation in inferior frontal areas. For multiplication, however, the increase of activation in the left angular gyrus indicates a switching of cognitive processes. Trained subtraction therefore seems to lead to faster and more efficient strategies, while trained multiplication showed a shift from quantity-based processing (supported by the areas along the intraparietal sulci) to more automatic retrieval (supported by the left angular gyrus). The same training method caused changes in brain activation patterns that depended on the given operation. The effects of learning on the brain therefore seem not only to depend on the method of learning but also on its content.