Myelodysplastic syndrome (MDS), is a group of heterogeneous disorders of hematopoietic stem cell colonies which is determined by incomplete hematopoiesis in one or more cell lines. The incidence increases with age and it has less been reported among patients under 50 years of age. The commonest form of MDS is sporadic, and familial occurrence of MDS is rare. Patients with familial MDS are younger at the time of diagnosis than individuals with sporadic disease and are faced with an unusual family history of more than one first-degree relative with MDS. In this study, we investigated a family with 16 members which has a family history of MDS in three consecutive generations. Cytogenetic and chromosome analyzes were performed on the 16 members of the family. Moreover, let-7a miRNA expression and its target gene, NRAS were evaluated compared to the control group. The karyotype analysis in this family shows two patients with abnormal karyotype, whereas expression of the let-7a and NRAS in this family showed a significant decrease compared to the control group. Regarding the decreased expression of let-7a in patient samples, this miRNA can be further considered as a marker for early diagnosis of MDS disease.