Finding the diagnosis in children with mental retardation and a normal karyotype, whether or not associated with dysmorphic features, is important for defining an eventual syndrome and for genetic counselling of the families. Telomeric re-arrangements may be a common and underestimated-to-date cause of non-syndromic mental retardation. Using a FISH-based approach combining subtelomeric probes, we report the detection of 4 cases of cryptic translocations t(2;10)(p25.3;q26.3), t(4;17)(p16.2;q25), t(4;20)(p16.2;q13) and t(5;7)(p15.3;q36) associated with MR and dysmorphic features. We discuss the usefulness of subtelomeric FISH in children with unexplained delayed psychomotor development, when the genetic cause remains unknown and the karyotype is normal.