BACKGROUND: Eating disorders (ED) are classified into Anorexia Nervosa, Bulimia Nervosa, and eating disorder not otherwise specified. Prospectively, the diagnostic instability within ED is high, but it is not clear which factors may account for this instability. So far, there is no evidence of whether psychiatric comorbidity may play a role in ED diagnostic crossover. We sought to determine possible influences of comorbidities of axis I and II on diagnostic crossover within ED. METHODS: Longitudinal data of 192 female patients were collected. All patients had a diagnosis of a current ED at study entry (baseline, T0). Diagnoses were re-established both 12 months (T1) and 30 months (T2) after T0. Comorbid psychiatric diagnoses were grouped into axis I and axis II according to DSM-IV. RESULTS: Patients with instable ED diagnoses had lifetime axis-I comorbidity more frequently than patients with stable ED diagnoses (χ2 = 4.74, df = 1, p < 0.05). Post-hoc exploratory tests suggested that the effect was mainly driven by affective disorders like major depression. There was no difference for axis-II comorbidity between stable and instable diagnostic profiles. CONCLUSIONS: Following previous reports of diagnostic crossover in ED, the present investigation points to an influence of a life-time psychiatric comorbidity, in particular of axis I, on follow-up diagnoses of ED. Comorbid affective disorders like major depression might facilitate a switching between clinical phenotypes. The understanding of mechanisms and causes of the symptoms fluctuation will be subject of future studies.