Objectives. The objective of this study was to investigate symptoms and predicting factors of depression and anxiety among reindeer-herding Sami in Sweden. Study design. A total of 319 reindeer-herding Sami (168 men, 151 women) were compared with urban and rural reference populations comprising 1,393 persons (662 men, 731 women). Methods. A cross-sectional questionnaire study on mental health, which included the Hospital Anxiety and Depression Scale (HADS). Data were analysed with regard to population, gender, age group, education and work-related stress. Results. The Sami population disclosed higher mean values for both depression and anxiety than the reference groups, with Sami men reporting the highest rates. Work-related stress was associated with anxiety and depression in the Sami group. Conclusions. By comparing Sami men and women with reference groups of men and women living in urban and rural areas in northern Sweden, this study identified that reindeer-herding Sami men require special attention with regard to mental health problems.