In Mediterranean lagoons, macrophytes often surpass phytoplankton as the most important primary producers. Less frequently, phytoplankton dominates throughout the year, thus knowledge of its dynamics is relatively limited and scattered. In this study, we assessed over two years the dynamics of phytoplankton assemblages, including potential harmful algal species (HAS), in relation to environmental changes in the phytoplankton-dominated Cabras Lagoon (Sardinia, Italy). The lagoon was characterised by uniform spatial conditions, wide temporal variations in salinity (40 PSU) and high nutrient availability. Phosphorus was highest in summer, possibly recycled within the system, while dissolved inorganic nitrogen increased in winter and spring due to watershed discharge. Chlorophyll a, positively correlated with nutrients and rainfall, showed a typical bimodal pattern with summer-winter blooms. Modifications in phytoplankton composition strongly correlated with extreme weather events, such as intense rainfall. This generated an abrupt salinity decrease that, combined with high nutrient availability, favoured the dominance of Cyanophyceae of reduced cell size, such as Cyanobium and Rhabdoderma species. We suggest that the prolonged and intense dominance of Cyanophyceae, added to other HAS, has a negative impact on the primary economic activities of the lagoon, such as fishery, and generally on the whole lagoon functioning.