This paper presents available information on the comorbidity of narcissistic personality disorder (NPD) and pathological narcissism with major mental illness. A review of empirical studies reporting on the prevalence of NPD in Axis I disorders, and of theoretical and clinical literature on narcissistic pathology in major mental illness, forms the basis for an analysis of this interface. The results show that prevalence rates of NPD in Axis I disorders rarely exceed those found in the general psychiatric or personality disorder populations (i.e., less than 22%). NPD was found at high rates in individuals with a substance use disorder (12-38%) or bipolar disorder (4-47%); it was present at very low rates or absent in persons with obsessive-compulsive disorder. Higher prevalence rates were reported in the studies that used the Millon Clinical Multiaxial Inventory I or II than in those that employed the Structured interview for DSM-III Personality Disorders or the Structured Interview for DSM-III-R Personality Disorders--Revised. There is no evidence implicating a significant relationship between NPD and any specific Axis I disorder. A comparison of theoretical and clinical studies with empirical ones reveals major differences in the views regarding the presence and significance of NPD in Axis I disorders. However, the results highlight trends of interacting comorbidity between NPD and substance use disorders, bipolar disorder, depression, and anorexia nervosa.