Stories are often used in health communication because of accumulating evidence of their potential to affect people’s attitudes and health behavioral intentions. Similarity between the reader and the story’s protagonist appears to positively influence narrative persuasion, but the exact role of similarity on persuasive outcomes is debated, as some research finds clear effects of similarity manipulations whereas others do not. Possibly, these mixed results were found because the similarity manipulations were not always relevant to the topic of the story. We conducted an experiment (N = 582) in which we varied the age and gender of the protagonist, features that were of central relevance to the story’s topic, namely breast cancer versus testicular cancer. There were two groups of participants: 324 students (mean age: 21.46 years) and 258 older adults (mean age: 56.83 years). Age similarity (but not gender similarity) had an effect on identification with the protagonist, transportation (i.e. the experience of being absorbed into a story), and the intention to donate, but only for students. For older adults, age or gender of the protagonist did not seem to matter, as nearly no differences in persuasive measures were found. As far as the underlying mechanism is concerned, the results of structural equation modeling showed that the concept of ‘perceived similarity’ would be a relevant addition to models of narrative persuasion, as it was significantly related to the narrative processes of transportation and identification, which, in turn, predicted attitudes and behavioral intentions, both directly—in the case of transportation—or indirectly, via the emotion of compassion. We conclude that both manipulated and perceived similarity are important for narrative persuasion, and that it should be kept on the research agenda of health communication.