The medial prefrontal cortex (MPFC) is regarded as a region of the brain that supports self-referential processes, including the integration of sensory information with self-knowledge and the retrieval of autobiographical information. I used functional magnetic resonance imaging and a novel procedure for eliciting autobiographical memories with excerpts of popular music dating to one's extended childhood to test the hypothesis that music and autobiographical memories are integrated in the MPFC. Dorsal regions of the MPFC (Brodmann area 8/9) were shown to respond parametrically to the degree of autobiographical salience experienced over the course of individual 30 s excerpts. Moreover, the dorsal MPFC also responded on a second, faster timescale corresponding to the signature movements of the musical excerpts through tonal space. These results suggest that the dorsal MPFC associates music and memories when we experience emotionally salient episodic memories that are triggered by familiar songs from our personal past. MPFC acted in concert with lateral prefrontal and posterior cortices both in terms of tonality tracking and overall responsiveness to familiar and autobiographically salient songs. These findings extend the results of previous autobiographical memory research by demonstrating the spontaneous activation of an autobiographical memory network in a naturalistic task with low retrieval demands.