The relationship between alexithymia assessed by the Toronto Alexithymia Scale (TAS) and the five-factor model of personality measured by the NEO Five-Factor Inventory (FFI) was investigated in a group of psychiatric outpatients (n = 114) and normal volunteers (n = 71). When controlling for depression, the domains of neuroticism, introversion, and low openness predicted alexithymia. These three dimensions accounted for 57.1% of the explained variance in the patient cohort and 38.1% in the volunteer group. In the patient cohort, neuroticism contributed the majority of explained variance, which may reflect the state effect of distress that elevates neuroticism. Introversion was the most significant predictor in the volunteer group. These data suggest alexithymia is a unique personality trait that is not fully explained by the five-factor model of personality.