Previous studies have shown activation of right orbitofrontal cortex during judgments of odor familiarity. In the present study, we sought to extend our knowledge about the neural circuits involved in such a task by exploring the involvement of the right prefrontal areas and limbic/primary olfactory structures. Fourteen right-handed male subjects were tested using fMRI with a single functional run of two olfactory conditions (odor detection and familiarity judgments). Each condition included three epochs. During the familiarity condition, subjects rated whether odors were familiar or unfamiliar. During the detection condition, participants decided if odors were present. When contrasting the familiarity with the detection conditions, activated areas were found mainly in the right piriform cortex (PC) and hippocampus, the left inferior frontal gyrus and amygdala, and bilaterally in the mid-fusiform gyrus. Further analyses demonstrated that the right PC was more strongly activated than the left PC. This result supports the notion that the right PC is preferentially involved in judgments of odor familiarity.