Especially in situations where it might be favorable for the patient to dissimulate the existing alcohol problem, ‘objective’ laboratory tests can be helpful. In this study we report validation of the two combinations DOVER (DOctor VERified) and QUVER (QUestionnarie VERified) of the biological markers percent carbohydrate-deficient transferrin (%CDT) and gamma-glutamyl-transferase (γ-GT) to detect patients that have been identified by their physicians with at-risk drinking behavior. Fifty-eight general practitioners (GPs) participated at two study sites in South-West Germany. Patients filled in a questionnaire that included the alcohol use disorders identification test (AUDIT) and gave a blood sample. The GP recorded his/her assessment about the presence of an alcohol-related disorder in the patient. Receiver operating characteristics (ROC) analyses of the marker combinations DOVER and QUVER were performed. A total of 2940 patients participated in the study, of which 2496 completed data sets that could be used for further analysis. The area under the curve (AUC) of 79.5% for DOVER and 77.2% (QUVER) are in a higher range than the values for gamma%CDT (75.7%) or γ-GT (72.5%) and %CDT (64.5%) and suggest superiority of the proposed marker combinations. Cross-validation results were almost identical with 76.6% and 73.3% for DOVER and QUVER, respectively. Our analysis demonstrated that the combination of the markers γ-GT and %CDT with the physician’s judgement of the condition as reference was superior to the use of single markers.