Cystic fibrosis (CF) gene is observed to have the highest frequency of mutations in Caucasian population (more then 1400). A group of relatively common CF alleles occurs in certain populations, but majority of mutations are rare, being private or limited to a small number of individuals. Since 1996. as a part of routine postnatal CF diagnostic procedures, we have been analyzed DNA samples of 179 patients for the presence of molecular defects in CFTR gene. Results showed that 18 different mutations accounted for 82.41% of CF alleles. In two patients DGGE patterns of exon 10 had unusually movement, and after sequencing of PCR-amplified genomic DNA it were shown that they had complex alleles. Both patients, although unrelated, were compound heterozygous for F508del inherited from one parent, and S466X with R1070Q in cis, inherited from the other parent. They were 7 years old females and had similar clinical symptoms with age at diagnosis before first year of life. Chloride sweat values were more then 91mmol/L, they were PI since birth, with obstructive lung disease and chronic cough. In both cases phenotype was severe despite the fact that one of the mutations (R1070Q) belongs to class IV (mild mutations). Both girls were from the same region of our country, which sugge st that their families might have common ancestor from whom they inherited this unusual allele. Complex alleles, in which more than one CFTR mutation is present in cis are very rare, but have been observed in some populations. In this group of analyzed CF patients frequency of double-mutant alleles was 1.12%, suggesting that they might be more common than expected in our country. These findings are important cause of their implication for molecular diagnosis and genetic counseling of families at risk.