<p>Inducing mutation is one of the strategies for creating novel genotype-creating, which is fundamental to genetic studies and genetic improvements of a wide range of species including microalgae. Except a few model and intensively studied species, most of microalgae in cultivation originate usually from single cells and are extremely poor in genetic variation. Certain of microalgae reproduce asexually while others reproduce sexually with uncontrollable or less understood sexual processes. Only a small number of microalgae reproduce under controllable conditions. Inducing different genotypes (mutation) is highly appreciated by microalgal geneticists, elite strain developers and microalgal growers. Zeocin has been widely using as a selection marker in the genetic manipulation of eukaryotes. It breaks DNA and generates both single and double strand breaks of DNA (DSBs). Short insertion/deletion (InDel) may be produced during DSB repairing. Such performance of Zeocin offers us a novel approach toward mutating microalgae. In this mini review, we introduced the performance of Zeocin in breaking DNA, described the potential of Zeocin as a novel mutagen and outlined tentative Zeocin mutation trials among diverse species including microalgae. Zeocin promises to be a novel, applicable and convenient mutagen creating microalgal mutants.</p>