Tensile fatigue specimen of G20Mn5 and G22NiMoCr5-6 were tested to quantify the influence of internal defects on the fatigue resistance of cast steel components. Defects with varying sizes, geometric shapes and distribution were enforced by influencing the solidification and recorded by computer tomography (CT). Besides the characteristics of the detected cavities, the surrounding fungoid microstructure is classified and evaluated. Later the specimens were tested under cyclic tension and S/N-curves are derived. These data form the basis for extensive numerical simulations of the damage process and the crack growth of every individual specimen. Both processes are affected by the local multiaxial stress states and have their origin in the inside of the specimen. For validation, knowledge of the crack initiation time and propagation properties are essential. Therefore, all specimens respectively the properties of the internal defects are monitored during testing with three different state-of-the-art non-destructive testing (NDT) methods. Background and application of these NDT techniques are described within this paper. Finally, fracture surface analyses show different failure modes and provide further information for model validation.