BACKGROUND. In LI-RADS version 2018, observations showing at least one of five targetoid appearances in different sequences or postcontrast phases are categorized LR-M, indicating likely non-hepatocellular carcinoma (HCC) malignancy. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement for LI-RADS targetoid appearances among a large number of radiologists of varying experience and the diagnostic performance of targetoid appearances for differentiating HCC from non-HCC malignancy. METHODS. This retrospective study included 100 patients (76 men, 24 women; mean age, 58 ± 9 [SD] years) at high risk of HCC who underwent gadoxetic acid-enhanced MRI within 30 days before hepatic tumor resection (25 randomly included patients with non-HCC malignancy [13, intrahepatic cholangiocarcinoma; 12, combined HCC-cholangiocarcinoma]; 75 matched patients with HCC). Eight radiologists (four more experienced [8-15 years]; four less experienced [1-5 years]) from seven institutions independently assessed observations for the five targetoid appearances and LI-RADS categorization. Interobserver agreement and diagnostic performance for non-HCC malignancy were evaluated. RESULTS. Interobserver agreement was poor for peripheral washout (κ = 0.20); moderate for targetoid transitional phase or hepatobiliary phase appearance (κ = 0.33), delayed central enhancement (κ = 0.37), and targetoid restriction (κ = 0.43); and substantial for rim arterial phase hyperenhancement (κ = 0.61). Agreement was fair for at least one targetoid appearance (κ = 0.36) and moderate for at least two, three, or four targetoid appearances (κ = 0.43-0.51). Agreement for individual targetoid appearances was not significantly different between more experienced and less experienced readers other than for targetoid restriction (κ = 0.63 vs 0.43; p = .001). Agreement for at least one targetoid appearance was fair among more experienced (κ = 0.29) and less experienced (κ = 0.37) reviewers. Agreement for at least two, three, or four targetoid appearances was moderate to substantial among more experienced reviewers (κ = 0.45-0.63) and moderate among less experienced reviewers (κ = 0.42-0.56). Existing LR-M criteria of at least one targetoid appearance had median accuracy for non-HCC malignancy of 62%, sensitivity of 84%, and specificity of 54%. For all reviewers, accuracy was highest when at least three (median accuracy, 79%; sensitivity, 68%; specificity, 82%) or four (median accuracy, 80%; sensitivity, 54%; specificity, 88%) targetoid appearances were required. CONCLUSION. Targetoid appearances and LR-M categorization exhibited considerable interobserver variation among both more and less experienced reviewers. CLINICAL IMPACT. Requiring multiple targetoid appearances for LR-M categorization improved interobserver agreement and diagnostic accuracy for non-HCC malignancy.