Shiga toxin-producing Escherichia coli (STEC) strains belong to the group of pathogens that cause bloody diarrhea and hemorrhagic colitis with often severe complications. The main problem with human pathogenic E. coli strains, including STEC, is a wide spectrum of phenotypes and clinical manifestations. It is related to a variety of exchangeable genetic elements, like plasmids, bacteriophages, transposons and pathogenicity islands, that take part in horizontal gene transfer which influences creation of new dangerous bacterial strains. A good example of this phenomenon is a novel Shiga toxin-producing E. coli O104:H4 serotype that was associated with a widespread and severe foodborne disease outbreak in Germany in 2011. The O104:H4 strain was created by a number of horizontal gene transfer events between two distinct pathogens, resulting in the emergence of the new, atypical strain. That outbreak proved that also rare and unusual serotypes of STEC may be a significant risk factor and that the procedures recommended for STEC detection were not suitable to deal with this kind of pathogens. With respect to new combinations of chromosomal and extrachromosomal elements in susceptible bacterial hosts, epidemics and frequent human infections caused by STEC strains, we suggest that more attention should be paid to the development and improvement of diagnostic methods. It is difficult to determine STEC bacteria by general microbiological, biochemical and immunological assays, because strains can vary dramatically in their phenotypic and serotypic properties. It is postulated that standardized genetic tests, based on detection of features most frequently presented by STEC, particularly those located on easily exchangeable elements (such as Shiga toxin-encoding phages), can be more adequate for STEC detection.