• PURPOSE: To evaluate trends in liver function tests before detection of liver metastases from uveal melanoma. • DESIGN: Retrospective, comparative, observational case control study. • Methods Setting: The Israel uveal melanoma center at the Hadassah University Hospital. Patient Population: A total of 307 uveal melanoma patients who were diagnosed with uveal melanoma and followed between the years 1988 and 1998. Of them, 30 metastatic patients who had regular follow-up by liver function tests (LFTs) and liver imaging were included in this study. Eighty nonmetastatic patients were randomly chosen as controls. Observation Procedure: The medical records of the metastatic and control groups were reviewed documenting LFTs and liver imaging results. Main Outcome Measures: The mean level of each LFT, its sensitivity, specificity, and likelihood ratio at various time periods before the detection of metastases by liver imaging. • RESULTS: At the time of diagnosis of liver metastases by imaging, 50% of patients had at least one abnormal LFT (compared with only 5% of the control group). While no change was noted in the mean serum levels of bilirubin, mean lactate dehydrogenase (LDH), alkaline-phosphatase, gamma glutamyl transpeptidase (γGTP) aspartate-aminotrasferase, and alanine-aminotrasferase levels seem to rise, even within normal limits, during the 6 months before the detection of metastases. Based on likelihood ratios, alkaline-phosphatase and lactate dehydrogenase were the most predictive tests. Lactate dehydrogenase and aspartate-aminotransferase were already predictive at 80% of the upper normal limit, whereas alkaline-phosphatase and γ-glutamyltransferase were most predictive at the upper normal limit. • CONCLUSIONS: Monitoring the changes in selected LFTs, even within normal limits, can help predict metastatic uveal melanoma.