In this study, we aimed to investigate the causes of liver test abnormalities in newly diagnosed patients naive to anti-tumoral therapy. This study included a total of 490 patients with ALT levels > 5X ULN on liver function tests at the initial presentation to our clinic. Data from 247 (50.4%) patients diagnosed with cancer (cohort A) and 243 (49.6%) patients without cancer (cohort B) were compared with regard to the etiology of liver test abnormalities and the risk factors. The most common etiological factor in cohort A was presence of liver metastasis (31.2%, = 77). In the comparison of the two groups with regard to etiological factors; the rates of liver metastasis 31.2% vs 0%, (  < 0.001), drug-induced liver toxicity 30/4% vs 19.8%, (  = 0.007), pancreaticobiliary pathology 21.5% vs 14%, (  = 0.03) and chronic viral hepatitis 14.2% vs 7.4%, ( = 0.02) were higher in the cohort A. The rate of NAFLD was higher in the cohort B 6.9% vs 42.2% (  < 0.001). In our study, the most common cause of liver test abnormalities was the presence of liver metastasis in cohort A and NAFLD in cohort B.