Cell counts are the standard measure to quantify harmful algae and the basis for decisions on measures necessary to protect human health. Molecular detection methods have been developed for a range of algal species and genera, but these methods generally quantify DNA or RNA, and corresponding cell numbers are inferred based on the assumption that the cellular nucleic acid content is constant over time and in different conditions. Here, we tested this assumption for ichthyotoxic flagellates of the genus Pseudochattonella (Dictyochophyceae) under different light, temperature, salinity, and nutrient conditions. Our results show changes in cellular RNA contents of nearly one order of magnitude depending on the condition and also the time of exposure, rendering it difficult to anticipate per-cell RNA yields even if environmental conditions are known. However, cellular RNA content was positively correlated with cell size and growth rate across our experiments, and total RNA was comparable to cell number as a predictor for total biovolume. These results demonstrate the importance of considering the variability of RNA levels for comparisons with cell counts and provide a valuable aid for the interpretation of data from RNA-based detection methods.