Objective: Worldwide, cancer is the second most frequent cause of death after the ischemic heart disease. Lifetime prevalence of psychiatric co-morbidities in cancer patients is 30-40%. Major depression is the most prevalent psychiatric disorder in patients with cancer. Major depression has a negative effect on quality of life, self-care, treatment compliance, prognosis, and treatment response of the cancer patient. In this study, we evaluated the prevalence of major depression in patients with cancer and the related factors which might affect this co-morbidity. Methods: Hundred patients with cancer (53 men and 47 women) who attended to oncology outpatient units were recruited to the study. Participants were assessed with 'Structured Clinical Interview for DSM-IV (SCID) - Mood Disorders Module' and 'The Questionnaire for the Assessment of Patients with Cancer'. Results: The prevalence of major depression in patients with cancer was 22%. The prevalence of major depression was higher in women than in men. Insomnia was found in 50% of patients. Insomnia was recognizedin 20% of patients with breast cancer and 15% of patients with lung cancer. Suicidal ideation was found in 11% of the patients with cancer. The prevalence of suicidal ideation increased with age and it decreased as the disease progressed. Conclusion: Major depression is a frequent psychiatric problem in the patients diagnosed with cancer. By reason of frequency, early recognition of major depression and the related factors will provide appropriate treatment. The frequency of suicidal ideation is even important in this population. Psychosocial support and psychiatric treatment approaches should be the focus of further attention in oncology clinics.