The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was published in 2001 by non-oncologic societies and later endorsed by the US Food and Drug Administration. A simplified GRADE adaptation scale offered two grades of recommendation: strong and weak. GRADE has been used by the European Association for the Study of the Liver (EASL) in hepatocellular carcinoma to evaluate clinical recommendations. Other oncologic societies such as ESMO used a different grading system to grade clinical recommendations in metastatic colorectal cancer (mCRC). Despite it, the levels of evidence in all these grading systems have important weaknesses to adequately interpret the whole-body of evidence in medical oncology. First, terms such as large, randomized trials and with good quality methodology introduce confusion if we do not objectively define the concept of large and good quality methodology. Second, not all randomized clinical trials (RCTs) are analyzed to support recommendations. In addition, different RCTs could have contradictory results, which are tough to analyze. Third, prospective observational studies are ranked below small, randomized trials or large randomized clinical trials with bias suspicion  or just missed in other grading classifications . It is important to acknowledge that methodology for causal inference from real-world data has evolved substantially in the last years . Therefore, the strength of evidence should be drawn from a comprehensive literature review and a careful evaluation of the study design, analysis, and interpretation, both in RCTs and in real-world data studies.