Abstract The fatigue strength of ductile cast iron is influenced by microstructural inhomogeneities (i.e., graphite, casting defects and matrix structures composed of different phases). In particular, the presence of small casting defects such as micro-shrinkage cavity can frequently cause not only significant deterioration but also large scatter in fatigue strength. Therefore, the laboratory fatigue tests with a limited number of small-sized specimens could result in a non-conservative estimation. For such a material, the prediction for the lower bound of the scatter in fatigue strength is essential from a practical perspective. In this study, a novel method is presented to predict the lower bound based upon the information of microstructural inhomogeneities and loading conditions. This method offers such an advantage that the lower bound can be reasonably predicted without conducting time-consuming fatigue tests. The predictive capability of the method was verified by comparing to the experimental results obtained in rotating-bending, torsion and combined tension–torsion fatigue tests of ductile cast irons with ferritic, pearlitic and bulls-eye structures.