Objective: The optical integration (OI) of monolithic CAD/CAM materials under 4 illuminations was evaluated using a standardized and clinically relevant method. Materials and methods: Eighteen inlays were manufactured and placed (glycerin gel). Standardized photos were taken under 4 illuminations (neutral white light direct and indirect illumination, cross-polarized light, fluorescent light). Six evaluators defined the optical integration score (OIS) as the "visibility" of the restoration (0 = worst OI, 4 = optimal OI). The intact tooth served as control. The null hypothesis was that different illuminations did not influence the OI of CAD/CAM inlays. One-way ANOVA, followed by Scheffe's post hoc, was applied (P = 0.05). Results: Neutral light direct illumination: OIS between 2.67 (IPS e.max CAD LT A1, ENAMIC A1) and 3.83 (IPS e.max CAD HT A1) with a mean of 3.28 (± 0.339). Indirect illumination: OIS from 1.00 (Paradigm MZ100 A1) to 2.41 (ENAMIC A1) with a mean of 1.88 (± 0.598). Fluorescent light: OIS between 0.75 and 3.25 with a mean of 1.67 (± 1.025). ENAMIC and VITA BLOCS Mark II showed the best optical integration in fluorescence. IPS e.max CAD, Paradigm MZ 100 demonstrated low fluorescence; Lava Ultimate high fluorescence. OI was influenced by different illumination. Conclusion: A simple method accessible to clinicians for additional evaluation of CAD/CAM materials in daily practice is presented. All materials showed excellent OI under direct illumination with neutral white light. The most pronounced differences in optical integration between tooth and evaluated materials were observed under fluorescent light.