Cyanobacteria havebeen identified as one of the most promising group producing novel biochemically active natural products. Cyanobacteria are a very old group of prokaryotic organisms that produce very diverse secondary metabolites, especially non-ribosomal peptide and polyketide structures. Though many useful natural products have been identified in cyanobacterial biomass, cyanobacteria produce also extracellular proteins related with NRPS/PKS. Detection of unknown secondary metabolites in medium was carried in the present study by a screening of 98 cyanobacterial strains. A degenerated PCR technique as molecular approaches was used for general screening of NRPS/PKS gene in cyanobacteria. A putative PKS gene was detected by DKF/DKR primer in 38 strains (38.8%) and PCR amplicons resulted from a presence of NRPS gene were showed by MTF2/MTR2 primer in 30 strains (30.6%) and by A3/A7 primer in 26 strains (26.5%). HPLC analysis for a detection of natural products was performed in extracts from medium in which cyanobacteria containing putative PKS or NRPS were cultivated. CBT57, CBT62, CBT590 and CBT632 strains were screened for a production of extracellular natural products. 5 pure substances were detected from medium of these cyanobacteria.