Purpose: To compare the masking ability of monolithic CAD/CAM veneers placed over different resin cement shades and substrate colors. Materials and Methods: Veneers were milled from four different monolithic CAD/CAM restorative materials: feldspathic ceramic (VMII), lithium disilicate ceramic (Emax CAD), zirconiareinforced lithium silicate ceramic (VS), and high-translucency zirconia ceramic (YZ-XT). Veneers were luted on natural tooth-colored (ND1) or discolored substrates (ND3 or ND5) using two different resin cement shades (opaque white or translucent). Each CAD/CAM material, resin cement shade, and substrate combination comprised 9 sample veneers (N = 216). Color parameters were obtained using a dental spectrophotometer before and after luting. Color differences (ΔE₀₀) were calculated using CIEDE2000 formula and compared to perceptibility (P = .81 ΔE₀₀ units) and acceptability (AT = 1.77 ΔE₀₀ units) visual thresholds. Color variation data were statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests with Bonferroni-Holm correction (α = .05). Results: The highest ΔE₀₀ value was obtained in the VMII group placed over a discolored substrate, followed by the Emax CAD, YZ-XT, and VS groups. The effect of material types on ΔE₀₀ values was significantly observed when the veneers were luted on discolored substrates using translucent resin cement (P < .05). Conclusions: Restorative material type, substrate color, and resin cement shade affect the masking ability of monolithic CAD/CAM laminate veneers.