Teaching fractions, and the concepts around them, has been proven to be a challenging task as multiple skills are required. This study examines the effectiveness of an intervention based on the "Response-to-Instruction" (RtI) model to students with math learning difficulties. The intervention was designed for teaching fractions, including both conceptual and procedural knowledge, to thirteen students with learning difficulties, attending mainstream middle schools in Greece. Its design was based on explicit instruction and on the Concrete-Representational-Abstract (CRA) strategy. The aim of this study is to evaluate the impact of the intervention and students' intra-individual improvement, using parametric statistical t-test of dependent samples. We used Single Case Design (SCD) with multiple baseline measures type A-B as an experimental design. We found a significant positive effect on students' performance in fractions and reliable data to monitor each student's responsiveness. The results of the present study converge with the findings in the literature that argue that explicit instruction and CRA strategy have a significant positive effect on developing mastery about fraction concepts in students with learning difficulties.