Large nuisance blooms of Didymosphenia geminata have become increasingly widespread in Patagonia. Although the first published account for South America was in 1964, reports of large growths in Chile and Argentina commenced around 2010. Since then, these blooms have been observed all along the Andes region to the south of parallel 42 S. General surveys are needed to help provide an explanation. Possibilities include one or more new genetic variants or responses of local populations to global environmental changes. Electron microscopy of material from the Argentinean Patagonia revealed marked differences between regions, though it is unclear how much local factors and/or variations in life cycle contribute. Thus, we are approaching the problem from a molecular perspective, which we hope will help to overcome this limitation. Initial studies showed that D. geminata seems to be highly recalcitrant to DNA extraction, thus hindering the survey of molecular markers. We have now developed an improved DNA extraction technique for Didymosphenia mats, which markedly outperforms other techniques. However, endpoint polymerase chain reaction analyses suggest the persistence of polymerase chain reaction inhibitors in the samples, highlighting the need of further improvements for quantitative studies.