Mammalian teeth are made of extremely hard and durable calcified tissues, which make them superb candidates for fossilization. The enamel crown, the outermost layer in the erupted tooth, precludes most microorganisms from entering into the underlying dentine and cementum, supporting tissues that are more vulnerable to microbial destructive action. Here we report the discovery of a single tooth of the late Eocene (ca. 35 Ma) North American basal lagomorph Megalagus, clearly containing filamentous and occasionally branching microfossils. The remarkably preserved microfossils are most similar to actinomycetes, gram-positive Eubacteria. We argue that these microorganisms were growing during the animal's life and thus document the first known tooth infection in placental mammals. Our findings provide insight into the initial development of mammal-dental pathogen interactions.