While humor typically involves a surprising discovery, not all discoveries are perceived as humorous or lead to a feeling of mirth. Is there a difference in the neural signature of humorous versus nonhumorous discovery? Subjects viewed drawings that were uninterpretable until a caption was presented that provided either: 1) a nonhumorous interpretation (or insight) of an object from an unusual or partial view (UV) or 2) a humorous interpretation (HU) of the image achieved by linking remote and unexpected concepts. fMRI activation elicited by the UV captions was a subset of that elicited by the humorous HU captions, with only the latter showing activity in the temporal poles and temporo-occipital junction (linking remote concepts), and medial prefrontal cortex (unexpected reward). Mirth may be a consequence of the linking of remote ideas producing high—and unexpected—activation in association and classical reward areas. We suggest that this process is mediated by opioid activity as part of a system rewarding attention to novel information.