Background: In Denmark, 42% of homeless people suffer from dual diagnosis, i.e. the co-occurrence of a substance use of alcohol and/or illegal substances and another psychiatric disorder. Dual diagnosis homeless patients often cause differential diagnostic difficulties and fail to receive effective treatment. A solid grasp of the role of substance use in these patients may inform the diagnostic decision and contribute to improve their treatment. Today, knowledge of these issues remains scarce. The purpose of this study was to explore substance use in homeless patients with mental disorders and their subjective perspectives on their substance use. Methods: 44 homeless dual diagnosis patients were included in the study. They were examined in interviews focusing on their substance use and their subjective perspective on their substance use. Results: The most frequently used substances were cannabinoids (70.5%) and alcohol (45.5%), followed by cocaine, sedative/hypnotics, and amphetamine. The finding suggests that substance use in dual diagnosis homeless patients is a complex phenomenon with most patients (56.8%) using multiple substances. While substance use seems to contribute to keep the patients homeless, substance use was also reported to play an important role in coping with life on the streets by offering social contact and some relief from a desperate situation. Conclusion: Substance use, mental disorder, and homelessness seem to be closely entangled, reinforcing each other and making it difficult to help these vulnerable patients. Diagnostic overshadowing may cause delays in adequate diagnosis and treatment of this group of patients.