OBJECTIVE: To characterize the composition, flexure resistance, and optical properties of a multilayer translucent zirconia in relation to its multi-transition zones. MATERIALS AND METHODS: A multilayer zirconia (5Y/4Y) and a conventional 3 mol% yttria partially stabilized zirconia (3Y) were investigated. Bar-shaped specimens were obtained from the enamel and dentin layers, and the vertical cross-section of 5Y/4Y (N = 10). A four-point flexural (σ RESULTS: The yttrium content and σ CONCLUSIONS: Different layers of multilayered zirconia have distinct compositions, which affect their mechanical and optical properties. The weak enamel layer compromises the mechanical properties of cross-sectional specimens. CLINICAL SIGNIFICANCE: The development of novel cubic-containing multilayer zirconia ceramics to produce monolithic restorations brings new challenges to dental clinicians and laboratory technicians. The CAD/CAM design of multilayered 5Y/4Y restorations should consider the esthetic and mechanical requirements of each clinical case, as different properties are found in the different layers of these materials.