Mutations are the best way to generate genetic variation, as they provide the raw material in which evolutionary forces, like natural selection, can act. However, mutations are not always able to change the apparent behaviour of an organism, instead, they are capable of providing normal and abnormal biological functions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a new and controversial biological scenario. Despite the hundreds of studies performed, to date, there is no specific treatment available. Several genomic and non-genomic mutations have been also reported, and due to its high genome size and mutation capacity, it can acclimatize to variable environments and has become the leading cause of high infection and mortality rates. This review outlines the possible pathways behind SARS-CoV-2 mutations.