In this study, the relationship between adolescents' difficulty in mathematics and reading and the influence on academic self-concept and school grades was examined. The participants (N = 585; 299 girls, 286 boys) were one age group of ninth-graders whose mathematics and reading skills were assessed at the end of comprehensive school at age 16 years. Five student profile groups were found using cluster analysis: best achievers, normal achievers (NA), the reading difficulty (RD) group, the mathematical difficulty (MD) group, and the learning difficulty (LD) group. Post-hoc tests revealed that the RD group and the LD group had a higher academic self-concept than the MD group. In school grades history, surprisingly, the NA group and the RD group performed equally well across all school grades. Students in the MD group performed as poorly as the LD group. The results emphasise the prolonged and generalised effects of especially MD on students' academic careers.