In large castings made of nodular cast iron, dross is not easy to detect with nondestructive testing (NDT) methods and reduces the static and cyclic fatigue strength of the material significantly, as shown in the example in figure 1. This causes a significant amount of work in foundries in removing dross or rejecting the complete component if a secure assessment of the component’s lifetime cannot be given. The aim of the reported work was thus to find appropriate methods to determine the characteristics of dross, such as its stiffness and density, in thick-walled nodular cast iron and to set up an assessment concept for the lifetime determination of components affected by dross. For the investigations, large cast blocks of EN-GJS-400-15 were cast with fields of dross in the upper side of the blocks. These blocks were investigated with different NDT methods, such as mechanized ultrasonic testing and magnetic particle inspection, to obtain information on the position and the characteristics of the dross. Subsequently, fatigue specimens and tensile specimens were removed from the cast blocks from the dross regions and from the baseline material without dross and were tested under strain control to determine the cyclic strain-based material behavior of the different specimens, with varying forms of dross. Additionally, all fatigue specimens were investigated with regard to their dross distribution using X-ray computer tomography, sulfur tests, and magnetic particle inspection. During the investigations, special attention was paid to the material stiffness, because this is significantly influenced by dross. Also, previous results on shrinkages in nodular cast iron showed good correlation between the material stiffness and the density measured in the specimen’s test volume. This correlation offers a link to NDT and a possibility to assess the influence of dross on the local fatigue strength.