Microcystins are cyclic peptide toxins with hepatotoxic and tumour-promoting properties which are produced in high quantities in freshwater cyanobacterial water blooms, and several studies have reported microcystin accumulation in fish with possible food transfer to humans. In this study, we provide the first comparison of liquid chromatography with single mass-spectrometric and with tandem mass-spectrometric detection for analyses of microcystins in complex fish tissue samples. Use of traditional single mass spectrometry (i.e. monitoring of ions with m/z 519.5 for microcystin-RR and m/z 995.5 for microcystin-LR) was found to provide false-positive responses, thus overestimating the concentrations of microcystins in the tissue samples. More selective tandem mass spectrometry seems to provide more reliable results. The concentrations of microcystins detected by tandem mass spectrometry in fish from controlled-exposure experiments were more than 50% lower in comparison with concentrations obtained by single mass spectrometry. Extensive analyses of edible fish parts-muscles (148 fish specimens from eight different species from five natural reservoirs with dense cyanobacterial water blooms)-showed negligible microcystin concentrations (all analyses below the limit of detection; limit of detection of 1.2-5.4 ng/g fresh weight for microcystin-RR, microcystin-YR and microcystin-LR in multiple reaction monitoring mode). Our findings have practical consequences for critical re-evaluation of the health risks of microcystins accumulated in fish.