OBJECTIVES: The objectives of this study were (1) to assess the bonding performance of a new auto-adhesive cement (RelyX Unicem, 3M ESPE) to enamel and dentin, using a standard micro-tensile bond strength (microTBS) test set-up, and (2) to evaluate the interaction of this material with dentin by means of high-resolution electron microscopy. METHODS: The microTBS of RelyX Unicem with and without prior acid etching was determined to enamel and dentin after 24 h of water storage and compared to the bonding effectiveness of the control cement (Panavia-F, Kuraray). In addition, diamond-knife cut interfaces of RelyX Unicem and Panavia-F bonded to dentin were examined using field-emission scanning (Fe-SEM) and transmission electron microscopy (TEM). RESULTS: The microTBS of RelyX Unicem to enamel was significantly lower than that of the control cement, whereas no significant difference was found when both cements were bonded to dentin. Acid etching prior to the application of RelyX Unicem raised the enamel microTBS to the same level as that of the control, but was detrimental for the dentin bonding effectiveness. The latter must be attributed to inadequate infiltration of the collagen mesh as revealed by Fe-SEM and TEM. Morphological evaluation additionally revealed that RelyX Unicem only superficially interacted with enamel and dentin, and that application using some pressure is required to ensure close adaptation of the cement to the cavity wall. SIGNIFICANCE: (1) RelyX Unicem should always be applied with some pressure, to ensure that the relatively high viscous cement intimately adapts to the cavity wall; (2) The cement only interacted superficially with dentin and enamel; (3) The best bonding effectiveness with this new auto-adhesive cement was obtained by selectively acid-etching enamel prior to luting.