Background The Major Depression Inventory (MDI) is a brief self-rating scale for the assessment of depression. It is reported to be valid because it is based on the universe of symptoms of DSM-IV and ICD-10 depression. The aim of the current preliminary study was to assess the reliability, validity and psychometric properties of the Greek translation of the MDI. Methods 30 depressed patients of mean age 23.41 (± 5.77) years, and 68 controls patients of mean age 25.08 (± 11.42) years, entered the study. In 18 of them, the instrument was re-applied 1–2 days later and the Translation and Back Translation made. Clinical diagnosis was reached with the use of the SCAN v.2.0 and the International Personality Disorders Examination (IPDE). The Center for Epidemiological Studies-Depression (CES-D) and the Zung Depression Rating Scale (ZDRS) were applied for cross-validation purposes. Statistical analysis included ANOVA, the Spearman Product Moment Correlation Coefficient, Principal Components Analysis and the calculation of Cronbach's α. Results Sensitivity and specificity were 0.86 and 0.94, respectively, at 26/27. Cronbach's α for the total scale was equal to 0.89. The Spearman's rho between MDI and CES-D was 0.86 and between MDI and ZDRS was 0.76. The factor analysis revealed two factors but the first accounted for 54% of variance while the second only for 9%. The test-retest reliability was excellent (Spearman's rho between 0.53 and 0.96 for individual items and 0.89 for total score). Conclusion The current study provided preliminary evidence concerning the reliability and validity of the Greek translation of the MDI. Its properties are similar to those reported in the international literature, but further research is necessary.