BACKGROUND: The Hopkins Symptom Checklist in 25 items (HSCL-25) helps to assess anxiety and depression in Primary Care. Anxiety and depression show considerable overlap in primary care. This self-administrated questionnaire is valid, reliable and ergonomic in the original US version. We have translated it into French. The aim of this study was to estimate the test characteristics of the HSCL-25, in its French version (F-HSCL-25), by comparing it to the Present State Examination-9 French version (F-PSE-9) and by determining its internal validity and dimensions. METHOD: Outpatients from three French General Practice settings (rural, semi-rural and urban) were recruited: approximately 20,000 outpatients among 17 GPs. Two groups were formed: F-HSCL-25 ≥1.75 and F-HSCL-25 <1.75. A validated cut-off score of > 1.75 was considered to indicate a clinically relevant level of symptoms of depression and anxiety. In order to obtain two balanced groups, a different method of randomization was chosen for each group. The F-PSE-9 was randomly administered to 1 in 2 patients in the F-HSCL-25 ≥1.75 group, and to 1 in 16 in the (much larger) F-HSCL-25 <1.75 group. The diagnostic performance was assessed and the test results obtained from both groups were compared with their F-PSE-9 results. RESULTS: Of the 1126 patients who completed the F-HCL-25, 886 joined the F-HSCL-25 <1.75 group and 240 the F-HSCL-25 ≥1.75 group. The overall prevalence of depression, using the F-HSCL-25, was 21% in these medical practices. The diagnostic performance of the F-HSCL-25 versus the F-PSE-9, the external criteria were as follows: Positive Predictive Value (PPV) 69.8%, Negative Predictive Value (NPV) 87%; Sensitivity 59.1%, and Specificity 91.4%. The Principal Component Analysis showed that F-HSCL-25 is a one-dimensional tool (anxiety and depression dimensions combined) with a Cronbach Alpha of 0.93. CONCLUSION: The F-HSCL-25 is an appropriate diagnostic tool for anxiety and depression in primary care in France due to its high specificity and high NPV. The HSCL-25 scale has a high eigenvalue. This pilot study will be extended throughout Europe; however, preliminary evidence suggests that the HSCL-25 is a reliable and suitable diagnostic tool for primary care.