Background: Comorbid psychiatric illness can undermine outcomes among homeless persons undergoing addiction treatment, and psychiatric specialty care is not always readily available. The prognosis for nonsubstance abuse psychiatric diagnoses among homeless persons receiving behaviorally-based addiction treatment, however, is little studied. Results: Data from an addiction treatment trial for 95 cocaine-dependent homeless persons (1996-1998) were used to profile psychiatric diagnoses at baseline and 6 months, including mood-related disorders (e.g. depression) and anxiety-related disorders (e.g. post-traumatic stress disorder). Treatment interventions, including systematic reinforcement for goal attainment, were behavioral in orientation. There was a 32% reduction in the prevalence of comorbid non-addiction psychiatric disorder from baseline to 6 months, with similar reductions in the prevalence of mood (-32%) and anxiety-related disorders (-20%) (p = 0.12). Conclusion: Among cocaine-dependent homeless persons with psychiatric comorbidity undergoing behavioral addiction treatment, a reduction in comorbid psychiatric disorder prevalence was observed over 6 months. Not all participants improved, suggesting that even evidence-based addiction treatment will prove insufficient for a meaningful proportion of the dually diagnosed homeless population. © 2006 Kertesz et al; licensee BioMed Central Ltd.