Hemoglobin disorders such as thalassemias and sickle cell anemias can be avoided by detecting carriers, ensuring genetic counseling and prenatal diagnosis. Nowadays Chorionic villus sampling (CVS amniocentesis, and cordocentesis are still the most widely used invasive sampling methods for prenatal diagnosis of the fetus. These traditional methods are associated with a risk of fetal loss. The revelation of cell-free fetal DNA (cffDNA) in maternal plasma and serum provides the opportunity of noninvasive prenatal diagnosis (NIPD). Different encouraging clinical applications have arose such as noninvasive identification of fetal sexing, fetal Rhesus D, and the determination of the paternal alleles in maternal plasma. The determination of the presence or absence of paternally inherited alleles in maternal plasma of sickle cell disease (SCD) and beta-thalassemia would allow the diagnosis of autosomal dominant diseases or the exclusion of autosomal recessive diseases of the fetuses, respectively. prenatal diagnosis of genetic diseases. Analysis of cffDNA in maternal plasma for NIPD has the advantage of being safer versus the invasive methods. Different technologies were used since the discovery of cffDNA for NIPD-especially high-resolution melting (HRM) analysis is one of those methods. Genotyping can be done with HRM without using labeled probes and more complex regions can be analyzed with unlabeled hybridization probes. High-resolution melting is a rapid and useful method to detect paternal alleles for the NIPD of SCD and thalassemias when the fetus has a risk for double heterozygote.