Purpose: To investigate whether (1) the curing mode and (2) the use of the corresponding or noncorresponding crown luting system have an impact on the microleakage of computer-aided design/ computer-assisted manufacture (CAD/CAM) composite crowns after chewing simulation. Materials and Methods: Two CAD/CAM composite blocks (Lava Ultimate [n = 20] and LuxaCam Composite [n = 20]) and their luting systems and curing modes (light curing [LC] or chemical curing [CC]) were investigated. A dye penetration test was used to detect the presence of microleakage. Results: Independently of the luting system, the LC groups showed a significantly lower microleakage compared to the CC groups (P .05). Furthermore, the CC groups exhibited a reduction of microleakage if the CAD/CAM block and luting system were from the same manufacturer. Conclusion: For the CC mode, the corresponding block and luting system should be used.